Ultrahigh-field (9.4T and 17.6T) magnetic resonance imaging of retinoblastoma: ex vivo evaluation of microstructural anatomy and disease extent
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 μm3 (FLASH) and 100x100x500 μm3 (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 μm3. 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 increase1-4 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.3

Conclusions

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

1. de Graaf P, Göricke S, Rodjan F, et al. Guidelines for imaging retinoblastoma: imaging principles and MRI standardization. Pediatr Radiol. 2012;42(1):2-14.

2. de Jong MC, de Graaf P, Noij DP, et al. Diagnostic performance of magnetic resonance imaging and computed tomography for advanced retinoblastoma: a systematic review and meta-analysis. Ophthalmology. 2014;121(5):1109-1118.

3. de Jong MC, de Graaf P, Brisse HJ, et al. The potential of 3T high-resolution magnetic resonance imaging for diagnosis, staging and follow-up of retinoblastoma. Surv Ophthalmol. 2015;60(4):346-355.

4. Beenakker JWM, van Rijn GA, Luyten GPM, Webb AG. High-resolution MRI of uveal melanoma using a microcoil phased array at 7 T. NMR Biomed 2013;26(12):1864–9.

5. Kashyap S, Sethi S, Meel R, et al. A histopathologic analysis of eyes primarily enucleated for advanced intraocular retinoblastoma from a developing country. Arch Pathol Lab Med. 2012;136(2):190-193

Figures

Figure 1. FLASH images (TR=36 ms, TE=4.2 ms, flip angle=12°, voxel=100x100x100 μm3 at 17.6 T) of an eye with a normal ciliary body (left) and an eye with a thickened dysplastic ciliary body and a mostly necrotic tumor (right).

Figure 2. RARE image (A; TR=7200 ms, TE=25 ms, flip angle=180°, voxel=100x100x500 μm3 at 17.6 T) and FLASH image (C; TR=36 ms, TE=4.2 ms, flip angle=20°, voxel =100x100x100 μm3 at 17.6 T) versus histopathologic slides (B and D). Arrows show examples of a ring of viable tumor around a central vessel (black central spot on MR) matching with viable tumor cells (purple) on histology with similar central vessel: “pseudo rosette”.

Figure 3. FLASH image (A; TR=36 ms, TE=4.2 ms, flip angle=12°, voxel=59x59x59 μm3 at 17.6 T) and (B) a matching histopathologic image showing a tumor mass and a detached retina. The arrow shows a subretinal tumor seed on the choroid.

Figure 4. Crop of a FLASH image (A; TR=36 ms, TE=4.2 ms, flip angle=12°, voxel=100x100x100 μm3 at 17.6 T) and (B) a matching histopathologic slide of tumor cells adjacent to the choroid (arrowheads) and a scleral vessel (arrows).



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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