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Resting State Functional Connectivity of the Hippocampus in Patients Receiving Radiation Therapy for Extra-Axial ....
Conference Paper · June 2015
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Resting State Functional Connectivity of the Hippocampus in Patients Receiving Radiation
Therapy for Extra-Axial Tumors
Marc C. Mabray MD1, Igor J. Barani MD2, Suresh E. Joel PhD3, Rakesh Mullick PhD3, Soonmee Cha MD1
1. University of California San Francisco Department of Radiology and Biomedical Imaging
2. University of California San Francisco Department of Radiation Oncology
3. General Electric Global Research
Introduction/Purpose! Results! !
Radiation therapy to the brain can result in brain toxicity and Both right and left hippocampal functional connectivity We encountered evidence of altered functional connectivity
radiation-induced cognitive decline with the hippocampus playing networks showed connectivity to the contralateral hippocampus between the pre- and post-radiation therapy brain in this study.
an important role.1, 2 Resting state functional MRI offers an and a few default mode network regions such as medial Specifically, we encountered decreased functional connectivity in
opportunity to study the effects of radiation therapy on the brain, temporal lobe and the anterior cingulate cortex (Figure top the right hippocampal network at the putamen in the post-
however there has been little research so far into this area.3, 4 panel). A statistically significant decrease in functional radiation networks as compared to the pre-radiation networks.
connectivity (p<0.009 after cluster-size correction) to the right Since both the hippocampus and the putamen are functionally
We aim to evaluate differences in the functional connectivity of
putamen was encountered in the post-radiation right complex and heterogeneous, investigation of the relationship of
the hippocampus in the pre- and post-radiation therapy brain by
hippocampus networks as compared to the pre-radiation this connectivity decrease to cognitive function decline is
evaluating resting state functional MRIs performed in patients E" F"
networks. warranted.
with extra-axial tumors. Our hypothesis is that there will be
decreased functional connectivity of the hippocampus in patients Interestingly, the left hippocampal network did not show any
that have received radiation therapy as compared to those that statistically significant difference post radiation. This right
have not. " lateralized change in functional connectivity may be related to
" radiation received at this location due to right side predominance
" of tumors in our cohort. However lateralized connectivity
changes of the right hippocampus has been previously reported in
the setting of Alzheimer’s disease.6
Materials and Methods! Further analysis with volumetric dosimetry data to determine the
radiation dose received in the right and left hippocampus is being
BOLD sensitized 2D EPI (TR/TE = 2000/30 ms; FA = 75°; FOV undertaken to explore the lateralization of the hippocampal
= 240x240x150 mm; voxel size = 3x3x4 mm) was used to acquire networks with subgroup analysis. !
functional MRI without an explicit task (resting state functional
MRI) prospectively on Radiation Oncology clinic patients Conclusion!
undergoing brain MRI on a 3 T scanner (GE Healthcare Systems).
"
We provide evidence of altered hippocampal functional
The above resting state fMRI (rs-fMRI) from 12 pre-radiation
connectivity in the post-radiation therapy brain as compared to
therapy and 27 post-radiation therapy MRIs in 33 patients (6 with
the pre-radiation therapy brain in a cohort of patients with extra-
pre and post imaging, 6 with pre imaging only, 21 with post
axial tumors.
imaging only) with extra-axial tumors treated with focal radiation
therapy (stereotactic radiosurgery) were analyzed in this study.
Further investigation into the functional connectivity of the post-
radiation therapy brain is warranted including correlation with
Acquired data were processed through a standardized processing
volumetric dosimetry data and neurocognitive function. This may
pipeline using custom built software from GE Global Research
provide insight into the effects of radiation therapy on brain
for motion correction, registration to anatomical images, Right hippocampal connectivity pre-RT (top), post-RT function and ultimately may affect ultimately improve radiation
registration to MNI atlas, physiological nuisance removal (using (middle), and regions showing decreased functional therapy planning. !
CompCor)5, spatial Gaussian smoothing (FWHM of 6 mm), and connectivity after RT (bottom). Note: Higher z-scores in the !
temporal band pass filtering to restrict signal bandwidth to 0.01 to post-RT networks in the mid panel are related to higher References:
0.1 Hz. Seed regions for left and right hippocampal area statistical power (larger n). 1.Gondi V, Hermann BP, Mehta MP, et al. Hippocampal dosimetry predicts
associated with the default mode network were drawn as a neurocognitive function impairment after fractionated stereotactic radiotherapy for
spherical region of 6 mm radius. benign or low-grade adult brain tumors. Int J Radiat Oncol Biol Phys
Discussion 2012;83:e487-493
2.Peiffer AM, Leyrer CM, Greene-Schloesser DM, et al. Neuroanatomical target
Pearson correlation coefficient of the mean time course of the The assessment of functional connectivity in the brain theory as a predictive model for radiation-induced cognitive decline. Neurology
seed region to every voxel’s time course was computed to create following radiation therapy with resting state functional MRI 2013;80:747-753
left and right hippocampal functional connectivity maps. Fisher’s may allow potential insight into the effects and complications of 3.Mickevicius N, Sabsevitz D, Bovi J, et al. Effects of Whole-Brain Radiation
radiation therapy. The irradiated brain may also offer the ability Therapy on Resting State Connectivity: A Case Study. International Journal of
transform was used to transform the connectivity values to z- Radiation Oncology • Biology • Physics;90:S325
scores. Pre-radiation functional networks were compared to post- to study the effects of selective lesioning by radiation therapy if 4.Sours C, Mistry N, Zhang H, et al. Feasibility Study Testing the Incorporation of
radiation networks using voxel wise t-tests with cluster size combined with volumetric dosimetry data. Resting State fMRI Data in Radiation Therapy Planning to Limit Dose to
constraints to account for multiple comparisons. Cognitive Function Networks in Patients With Primary Brain Tumors.
In this study we focused on extra-axial tumors treated with International Journal of Radiation Oncology • Biology • Physics;87:S254-S255
focal radiation therapy in order to help negate the effects of 5.Behzadi Y, Restom K, Liau J, et al. A component based noise correction method
infiltrative tumor involvement and tumor location on functional (CompCor) for BOLD and perfusion based fMRI. NeuroImage 2007;37:90-101
connectivity; these patients generally received lower radiation 6.Wang L, Zang Y, He Y, et al. Changes in hippocampal connectivity in the early
stages of Alzheimer's disease: evidence from resting state fMRI. NeuroImage
dose to the brain than patients with intra-axial tumors, which 2006;31:496-504
may make our findings more subtle.
! !
""
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