Justin Schumacher1, Li Jiang2, Jiachen Zhuo2, Howard Eisenberg3, Paul Fishman4, Dheeraj Gandhi2, and Rao Gullapalli2
1University of Maryland School of Medicine, Baltimore, MD, United States, 2Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, United States, 3Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, United States, 4Neurology, University of Maryland School of Medicine, Baltimore, MD, United States
Synopsis
MR Guided Focused Ultrasound (MRgFUS) is a novel
technique used to noninvasively lesion the brain for treatment of Parkinson’s
Disease (PD). In this study 12 PD patients with asymmetric motor symptoms underwent
MRgFUS pallidotomy and cortical thicknesses and subcortical volumes were
measured pre and post treatment. Subcortical gray matter volume increases were
observed 24 hours post treatment with bilateral decreases in basal ganglia gray
matter volume 3-6 months post treatment. Cortical thicknesses decreases were
observed in the frontal and temporal cortices of right-sided treated patients
3-6 months post treatment. These
regions may play a role in the management of dyskinesias.
Introduction
MR Guided Focused Ultrasound (MRgFUS) is a novel technique
used to noninvasively lesion the brain in diseases such as Essential Tremor,
Parkinson’s Disease (PD), and Neuropathic Pain1-3. While this
technique has been used effectively in early clinical trials, the resulting
changes on the human brain anatomy and structure following treatment are poorly
understood. Understanding the specific structural changes following MRgFUS
treatment are important clinically when assessing treatment options and
targeting therapy.Methods
Twelve PD patients with asymmetric motor symptoms and
without cognitive impairment underwent unilateral MRgFUS pallidotomy. Imaging
and clinical testing was performed before treatment, 24hr post treatment, and
up to six months post treatment. Our hypothesis was that MRgFUS induced lesions
result in changes to brain anatomy and structure, and therefore may be
attributed for the alleviation of symptoms. Cortical thickness and subcortical
volume measurements were estimated using the FreeSurfer image analysis suite
along with the longitudinal pipeline4,5. Both volumetric changes and
cortical thickness changes were assessed at two post treatment time points
compared to the pre treatment MRI. Paired t-tests were used to compare the pre and post treatment volumes and cortical thicknesses. Results
Demographics of the patients used in the MRgFUS study are
listed in Table 1. Structural analyses of the subcortical regions revealed
increases in overall gray matter volume at 24 hours post treatment followed by
decreases in overall gray matter volume 3-6 months post treatment (Figure 1). Bilateral
decreases in gray matter volume of the caudate, putamen, hippocampus, and
thalamus 3-6 months post treatment were observed (Figure 2). Structural
analyses of cortical thickness revealed decreases in contralateral frontal and
temporal cortices 3-6 months post treatment in the patient group that received right-side
treatment (Figure 3). Cortical changes were restricted to a smaller extent when
all patients were included. Discussion
Our preliminary results suggest MRgFUS treatment affects cortical
and subcortical gray matter structures. The overall subcortical gray matter
volume increases 24 hours post treatment may be attributed to edema following
ablation. However, this trend was not observed in each individual region
examined. The subcortical volume decreases and cortical thickness decreases at
3-6 months post treatment may be explained by nervous system atrophy that has
developed following treatment. The affected cortical regions involve the
primary motor cortex, executive function, and default-mode network, while the
affected subcortical regions involve the basal ganglia circuitry. All of these
regions may play a role in the management of dyskinesias. The volume decreases may
be related to atrophy via damaged fiber tracts or other remodeling processes that
may be triggered by the ablation.Conclusion
MRgFUS treatment has been shown to be effective in treating
a variety of neurological diseases, and research of the associated bioeffects
from MRgFUS has broad implications for use in clinical medicine. Results on
this small sample patients indicate changes in gray matter volumes following
ablation. This needs to be substantiated
in a larger population. Future work should also examine changes in white matter
tract integrity as well functional connectivity to correlate clinically with
the changes observed in these patients.Acknowledgements
The authors acknowledge, with appreciation, the University of Maryland School of Medicine Center for
Innovative Biomedical Resources (CIBR) and the Center for Translational Research in Imaging at Maryland
(CTRIM).References
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