Alexandre A Khrapitchev1, James R Larkin1, Stavros Melemenidis1, Peter E Thelwall2, and Nicola R Sibson1
1Department of Oncology, University of Oxford, Oxford, United Kingdom, 2Newcastle Magnetic Resonance Centre, Newcastle University, Newcastle upon Tyne, United Kingdom
Synopsis
The imaging of lungs with MRI is difficult owing to low proton
density. Imaging with hyperpolarized noble gases has overcome some of these
limitations but at great expense and effort. We have investigated damage caused
by radiation of mouse lungs using 19F MRI of perfluorohexane – a
cheap biocompatible liquid at room temperature. Using lungs filled with
perfluorohexane, we were able to obtain high resolution scans with comparable
SNRs to hyperpolarized xenon imaging and high resolution. These bright and
stable lung images provide a very sensitive tool to monitor the lung damage
development.Purpose
Imaging plays a major
role in assessment of pulmonary diseases and a broad spectrum of imaging techniques are
available. The main workhorse modality is still computed tomography (CT), which
allows fast and high-resolution assessment of the lung parenchyma and
surrounding structures. However, the soft tissue contrast and gain of direct
functional information is limited. MRI of the lung is difficult owing to the
low proton density of the tissue and, consequently, low signal intensity on
conventional
1H scans. At the same time, large differences in the
magnetic susceptibility of the lung tissue and air within the lungs,
respectively, reduces the signal strength even further. The hyperpolarization
of
3He or
129Xe is a viable, but expensive method of lung
MRI. To avoid these problems, we investigated the possibility of mouse lung imaging
by use of perfluorohexane, a biocompatible liquid at room temperature, and
19F MRI. Perfluorohexane has a very high oxygen solubility (41mL O
2/100g)
which makes "fluid-breathing", and therefore invivo experiments, a possibility.
19F has 83% of the
signal of
1H in MRI, which combined with the high
19F
concentration in the liquid gives a very high signal. Additionally, the absence
of fluorine in the body results in the lungs appearing bright with no
background signal [1].
Methods
As an application of
19F MRI imaging technique we have chosen
a mouse model of lung radiation damage. For the initial time-course study, 16 female
CBA mice (4 weeks old) were anaesthetized with isoflurane and the left lung
irradiated with a 20Gy dose over 2 minutes (SARRP, Xtrahl Ltd., UK). Starting
at week 6, one animal was sacrificed each week for ex-vivo MRI. Each mouse was
terminally anaesthetised and tracheotomized, then air in the lungs was replaced
with the perfluorohexane (C
6F
14). A dual tuned
1H/
19F
28mm birdcage coil (PulseTeq Ltd., UK) was used in a 7T spectrometer (Agilent
Inc., USA). MR images were acquired with standard 3D spin echo sequences:
matrix=128×128×128, FOV=25.6×25.6×25.6mm; TR=400ms, TE=4ms; Texp=1h50min. All
19F lung MR images were superimposed onto
1H MR
anatomical images. Lung images were bisected (left and right sides) for
statistical analysis. Throughout the time-course, mice were observed for
clinical signs, lung performance measured by plethysmography and behavior
monitored.
Results and discussion
High quality images
of the lungs were acquired using
19F MRI (Fig 1). The typical SNR is
broadly similar to those obtained from
129Xe hyperpolarization
experiments [2]. However, the voxel size in the
19F images (200µm)
was considerably smaller than voxels typically used in pre-clinical
129Xe
imaging (e.g. 625µm [3]), allowing improved visualization of lung structure.
The high image resolution allows qualitative analysis of disease progress: a left
lung post irradiation (Fig 1b) appears smaller and less intense than that of a
naïve mouse lung (Fig 1a), illustrating subtle anatomical changes invisible on
standard
1H MR images. Quantitative volumetric analysis highlights
early changes in relative lung volume (Fig 2a), whilst the mean signal
intensity of the irradiated lung (Fig 2b) reveals a highly significant
reduction, indicating lung damage starting long before signs begin to appear.
Conclusion
The ability to
monitor lung damage from early stages could be very important clinically and,
also, as a preclinical tool.
19F based perfluorohexane imaging gives
bright and detailed lung images, which allow visualization of structures not
apparent on proton MRI. This approach is more easily and cheaply implemented
than hyperpolarized gas setups and is immediately applicable in a range of
pre-clinical work.
Acknowledgements
This work was
supported by a Cancer Research UK core grant to Nicola Sibson (C5255/A12678).References
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