Rongbiao Tang1, E. Mark Haacke2, Yibin Zhang2, Qingrou Wang2, Naying He2, Weibo Chen3, Ke-min Chen2, and Fuhua Yan2
1Ruijin Hospital, Shanghai, China, 2Ruijin Hosptial, Shanghai, China, 3Philips Healthcare, Shanghai, China
Synopsis
Whole-brain radiotherapy (WBRT) is
often performed asynchronously with head
contrast-enhanced MRI examination (CEME) in patients with brain metastasis (BM). Data regarding T1
signal intensity (SI) changes in the dentate nucleus (DN) in BM patients after
WBRT and repeated exposure to gadolinium (Gd)-based contrast agents (GBCAs) are
lacking. In this study, we explored the correlation between T1 SI in the DN and
cumulative doses of linear GBCAs in BM patients
treated with WBRT.
Synopsis Whole-brain
radiotherapy (WBRT) is often performed asynchronously with head contrast-enhanced MRI examination (CEME) in patients with brain metastasis (BM). Data regarding T1
signal intensity (SI) changes in the dentate nucleus (DN) in BM patients after
WBRT and repeated exposure to gadolinium (Gd)-based contrast agents (GBCAs) are
lacking. In this study, we explored the correlation between T1 SI in the DN and
cumulative doses of linear GBCAs in BM patients
treated with WBRT.
Introduction
Gadolinium (Gd)-based contrast agents (GBCAs)
are commonly used in various clinical MRI examinations. Some previous studies
have demonstrated increased signal intensity (SI) in the dentate nucleus (DN)
and globus pallidus (GP) on unenhanced T1-weighted image (UT1WI) after repeated
exposure to GBCAs (1-4).
Histological examination has confirmed that the increased T1 SI in the deep
brain nuclei was caused by Gd deposition (5-7). Since free
Gd (Gd3+) is a heavy metal with toxicity, the Gd deposition in these
neurological functional nuclei has raised concerns about potential neurological
complications (6,
8-10).
Whole-brain
radiotherapy (WBRT) is a type of irradiation treatment delivered
to the entire brain over multiple visits. Due to this wide range of irradiation,
DNs are always included in the irradiation field of WBRT. Additionally, head contrast-enhanced MRI
examinations (CEMEs) are usually performed to assess whether there is BM when a
patient is diagnosed as cancer, especially lung cancer or mammary cancer. As a
result, patients with BM often receive multiple doses of GBCAs. Irradiation can
cause vascular damage to increase its
permeability, which may cause an accelerated leakage of Gd (11-14). The
accelerated leakage of Gd may further lead to an additional increase in T1 SI
in the DN after repeated exposure to GBCAs. Up to now, the extent of this
impact in patients with BM has not been investigated.
Methods
Patients: The electronic medical
records (EMR), PACS, and radiology information systems (RIS) were searched from
January 2010 to December 2018 to identify consecutive patients with BM who had
undergone WBRT and head CEMEs. Imaging
Protocol: All head CEMEs were performed with one of six MRI systems at
our institution. All MR examinations included an axial unenhanced T1WI sequence,
T2 FLAIR, and contrast-enhanced sequence (CES).
Data Analysis: The radiation doses (RDs) to the left and
right DNs were calculated. The SIs were measured using the Uniweb Viewer
software (EBM Technologies, China). All measurement screenshots were saved and were
all reviewed. Oval regions of interest (ROIs) were drawn as large as possible
within the DN, and the same size was used for CWM near the DN.
Statistical Analysis: All
analyses were performed with software SPSS and GraphPad Prism. Analysis included the
Shapiro-Wilk test, paired t test, Wilcoxon test, and Spearman correlation coefficient (r).
Results
WBRT plan maps for patients with BM were
shown in Figure 1. WBRT could cause Gd enhancement promotion within DNs as
shown in Figure 2. Comparisons of DN/CWML ratio and R between WBRT patients and control
patients were shown in Figure 3. Correlations of DN/CWML ratio or R with total number of IDs or number of
IDs after WBRT in Group 1 and Group 2 were shown in Figure 4 and Figure 5,
respectively. Demographics and patient characteristics by group were shown in
Table 1. Correlations between DN/CWML ratio or RFL dependent variables in WBRT group and control group
were shown in Table 2 and Table 3, respectively.
Discussion and Conclusion
The
progressive increase T1 SI in the DN was found to associate with the cumulative
IDs of GBCAs by many groups (4,
9, 10, 15). Our
results showed that T1 SI in the DN from control patients associated with the
total number of IDs, consistent with findings in other studies (2,
4, 6, 10). However, T1
SI in the DN from irradiated patients did not always correlate with cumulative doses
of GBCAs, as shown in the results from Group 2. In practical terms, when a
patient is diagnosed as lung cancer or mammary cancer, head CEMEs are usually performed to observe whether
there is BM. Meanwhile, WBRT will start for the patient when the BM is found. Therefore,
this uncertainty of irradiation time indicates that more total number of IDs does
not mean more number of IDs after WBRT. Because the increase rate of T1 SI improved
markedly after irradiation, the T1 SI was more likely to be determined by the
number of IDs after WBRT than the total number of IDs. This is different from
previous studies that have showed a continued significant relationship between
T1 SI in the DN and the total number of IDs in the irradiated patients with nasopharyngeal
malignancy or primary brain tumors (14,
16, 17). In these patients,
irradiation and head CEME are often started closely,
and thus the number of IDs after irradiation nearly equals to the total number
of IDs.
In order to reduce the potential neurological
complications, WBRT can be improved to confine the irradiation
field to the cerebrum if the brain metastases
occur only in the cerebrum. Besides, more precise
radiotherapy method may be used to prevent the irradiation exposure to the DNs.
Acknowledgements
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