Ming Zhao 1,2, Ouri Cohen2, Erez Nevo3, R.Gilberto Gonzalez2, and Jerome L. Ackerman2
1Department of Physics, University of Massachusetts Lowell, Lowell, MA, United States, 2Martinos Center, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, United States, 3Robin Medical, Inc., Baltimore, MD, United States
Synopsis
As part of a project to develop MR-induced RF heating of a
coagulable biomaterial for minimally invasive repair of vascular lesions, we investigate
the relationship between the heat coagulation behavior and MR relaxation
properties of egg white. This protein solution is a good model for the
analogous behavior of human serum albumin solution, an optimal (but expensive)
biomaterial for MR coagulation. We find that large changes in both T2
and the width of the magnetization transfer spectrum clearly indicate the
temperature at which the coagulation process occurs. T2 and MT
weighted MR images identify coagulated material in an aneurysm phantom.
Purpose
Magnetic
Resonance Mediated Radiofrequency Coagulation (MR coagulation) employs the RF
heating effect of the scanner to coagulate a biomaterial for repair of a
vascular defect.1,2 Coagulation of a protein biomaterial by
MR-induced RF heating is a novel means to effect repair of vascular defects
such as aneurysms or arteriovenous malformations. These defects are conventionally
repaired by surgical clipping or by filling/occluding with endovascularly
delivered wire coils.3 Our novel method, MR Coagulation, is intended
to achieve a comparable result by coagulating a thermosetting material (such as
a protein solution) delivered endovascularly by catheter and coagulated by
RF-induced heating of an intracatheter resonant wire antenna in the MRI scanner. The purpose of this study is to measure
the MR relaxation properties of a protein solution undergoing coagulation to
determine the most definitive MR methodology enabling the detection of
coagulation.
Human serum albumin (HSA) is the most
abundant protein in the blood, and has been used surgically to seal blood
vessels4 and to stem diffuse bleeding.5 In an image
guided MR coagulation procedure it is necessary to determine when coagulation
is complete using its MR characteristics. Egg white, essentially a 10 wt%
protein solution with about half the protein being ovalbumin, can be used as an
inexpensive substitute for HSA for investigating heat coagulation behavior and
MR relaxation properties. In this study, the MR relaxation properties of egg
white were studied as a function of temperature and degree of coagulation to
determine which contrast parameters would be most appropriate for imaging
studies. Additionally the coagulation of egg white by RF heating within a phantom
aneurysm in an MRI scanner was performed, and images were obtained based on the
relaxation parameters to test which parameter(s) would best ascertain the
coagulation state in vivo. Aneurysm experiments were carried out using saline
and water, and under conditions of flow and no flow.Methods
Experiments were performed on a Siemens 1.5 T (63.643
MHz) MRI scanner. A heating system was constructed to regulate the sample
temperature inside the magnet. Egg white in 10 mm NMR tubes was brought
to equilibrium at seven temperatures (20, 30, 40, 50, 60, 70 and 37 °C) in sequence. Separate
runs with fresh sample were performed for each relaxation time, using inversion
recovery, CPMG or magnetization
transfer (MT) pulse sequences to measure the water spin-lattice relaxation time
T1, spin-spin relaxation time T2,
or full width at half maximum (FWHM) of the MT spectrum respectively. Also,
relaxation parameters of raw egg white and egg white after coagulation at 70 °C were measured in the
MRI scanner at room temperature (20
°C) to determine optimum inversion time, echo time and
offset frequency for the pulse sequences. Finally coagulation of egg white
within a glass aneurysm phantom by RF heating inside MRI scanner was carried
out and images of the phantom aneurysm were taken to observe the state of
coagulation.Results
It was found that water T2 and MT
gave the most definitive indication of the change from uncoagulated at low
temperature to fully coagulated at 60 °C, while water T1 showed only
the expected gradual increase with temperature, and no response to coagulation.Discussion
In
pure liquid water, T1 exhibits a minimum value when the correlation
time for molecular reorientation matches the inverse of the Larmor frequency;
as the correlation time either increases or decreases, T1 will
increase. Unlike T1, T2 decreases as the correlation time
increases.4 In the presence of a soluble or coagulated protein, chemical
and spin exchange between bulk water protons, bound water protons and protein
protons complicates the relaxation behavior. Because T2 is affected
strongly by “static” frequency molecular motions, and spectral width of
magnetization transfer is affected by the spin exchange between free water and
bound protons, they are expected to be influenced strongly by the transition of
solution proteins from the ordered to the agglomerated state, as borne out by
our results. T2-weighted images are quick and easy to measure with
low SAR, but the images showed artifacts due to the rapid dephasing caused by
magnetic susceptibilities difference in different material.
Conclusions
Relaxation experiments show that egg white
protein fully coagulates at 60 ºC, which is relatively easy to achieve by
MR-induced heating of an intracatheter antenna. MR coagulation has potential as
a means to effect embolization of vascular defects. Means to produce a more
consolidated coagulum and to reduce downstream flow of particles need to be
developed. MT weighted imaging is expected to be the optimum method to
establish the coagulation condition of the biomaterial.Acknowledgements
This research is supported by the Center for the Integration of Medicine and Innovative Technology (CIMIT) grant 13-1180/grant W81XWH-09-2-001 from U.S. Army Medical Research and Materiel Command (USAMRMC) and NIH grants RR023009 and P41RR14075.References
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of vascular defects using MR radio frequency coagulation. Joint Annual Meeting,
International Society for Magnetic Resonance in Medicine and European Society
for Magnetic Resonance in Medicine and Biology, Milan, Italy, May 10-16, 2014.
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by MR coagulation. Seventh Annual Image-Guided Therapy Workshop, Cambridge, MA,
September 18-19, 2014.
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DW. Cerebral aneurysms. N Engl J Med 2006;355:928-939.
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