Marcus Christiaan de Jong1, Pim de Graaf1, Petra Pouwels1, Jan-Willem Beenakker2, Jeroen Geurts1, Annette C. Moll1, Jonas A. Castelijns1, Paul van der Valk1, and Louise van der Weerd2
1VU University Medical Center, Amsterdam, Netherlands, 2Leiden University Medical Center, Leiden, Netherlands
Synopsis
Staging of retinoblastoma – the most common
pediatric eye cancer – is currently performed in vivo at 1.5 or 3.0 T and
allows for images with voxel sizes <0.5x0.5x2 mm3. We performed ex
vivo ultrahigh-resolution MRI at 9.4 and 17.6 T of enucleated retinoblastoma
eyes. This method allowed us to generate high-resolution images (voxel size:
59x59x59 to 100x100x100 μm3) of different aspects of retinoblastoma
showing the potential of ultrahigh-resolution MRI for staging retinoblastoma
and gaining insight in anatomical details. Purpose
The primary purpose of our study was to
show the potential of ultrahigh-field MRI for detection of retinoblastoma tumor
extent and depicting tumor morphology by using prospectively obtained ex vivo
images and correlation with histopathology.
Materials and Methods
Six consecutive patients (all boys; median
age 5.5 months, range 2–14) with retinoblastoma, were prospectively included in
this study. In all patients one eye was enucleated: in three patients with
unilateral retinoblastoma the affected eye and in three patients with bilateral
retinoblastoma only the most affected eye. Median time between retinoblasoma diagnosis
and enucleation was 8 days (range 7–19).
Prior to enucleation in vivo MRI was performed using a 1.5T system with
a circular surface coil covering the affected eye. Ex vivo imaging was
performed again at 1.5 T and on two vertical 89-mm-bore magnets with field
strengths of 9.4 T (400 MHz) and 17.6 T (750 MHz). A Bruker Mini-0.5 gradient
system of 200 mT/m and transmit/receive birdcage radiofrequency coil with an
inner diameter of 38 mm was used on both systems. Eyes were placed in a 30-mm
plastic tube filled with Fomblin. On both systems 2D T2-weighted images (RARE)
and 3D FLASH T1-weighted images were obtained during over-night acquisition.
Resulting voxel sizes were 100x100x100 μm
3 (FLASH) and 100x100x500
μm
3 (RARE), 2.6 cm field of view (FOV). Additional small FOV (1.5
cm) detail images of tumor tissue were obtained with a voxel size of 59x59x59
μm
3. After ex vivo imaging the eyes were histopathologically
analyzed and matched with MRI findings. With multiplanar reconstruction we matched
MR images with hematoxylin and eosin stained histopathologic slides.
Results
Figure 1 shows an example of a case with a dysplastic
ciliary body and pigment dispersion compared to a case with a normal ciliary
body. We were able to correlate various aspects of intraocular retinoblastoma
as can be seen on histology with ultrahigh-field MR images. Calcifications and necrotic
areas can be distinguished and matched with histopathology. An example of an
eye with extensive necrotic areas and numerous viable pseudo rosettes presenting
as a ‘geographical pattern’ on both MR and histopathology images (figure 2).
Figure 3 shows an image with a small FOV of a tumor, detached retina and a
small subretinal tumor seed adjacent to the choroid. Finally we show MR images
of tumor in close proximity to the choroid, but no invasion yet (figure 4);
this figure also shows a vessel through the sclera.
Discussion
An important limitation of imaging at such
high field strengths is that it can only be performed ex vivo. Due to the small
diameter of the bore in vivo imaging is not possible at this moment, but it
does demonstrate the potential of ultrahigh-resolution imaging compared to
histopathology. An advantage of this technique is, however, that – contrary to
histopathology, which is usually performed on selected parts of the eye – the
entire eye can be sampled and as such might be useful additional to
histopathologic analysis, particularly for detection of choroidal invasion. MRI
technology will continue to evolve in the future and the image quality and resolution
of normal clinical MR systems will also increase
1-4 Poorly differentiated tumors with extensive necrosis have been
linked to metastatic risk factors such as tumor invasion into the choroid,
sclera or optic nerve.
5 More detailed information about tumor differentiation might be
helpful for disease prognosis and might help tailor therapeutic regimens.
3Conclusions
Ex vivo imaging of retinoblastoma shows the
possibilities of ultrahigh-resolution MRI for various aspects of disease
staging, gives insight in small anatomical details and might reduce sampling
error. Improved disease staging (in vivo and ex vivo) with more detailed
imaging can potentially improve treatment decisions.
Acknowledgements
No acknowledgement found.References
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