title: Diffusion-sensitized ophthalmic magnetic resonance imaging free of geometric distortion at 3.0 and 7.0 T: a feasibility study in healthy subjects and patients with intraocular masses.
abstract: OBJECTIVE
  This study is designed to examine the feasibility of diffusion-sensitized multishot split-echo rapid acquisition with relaxation enhancement (RARE) for diffusion-weighted ophthalmic imaging free of geometric distortions at 3.0 and 7.0 T in healthy volunteers and patients with intraocular masses.
  
  
  METHODS
  A diffusion-sensitized multishot split-echo RARE (ms-RARE) variant is proposed as an alternative imaging strategy for diffusion-weighted imaging. It is compared with standard single-shot echo planar imaging (EPI) and readout-segmented EPI in terms of geometric distortions in a structure phantom as well as in vivo at 3.0 and 7.0 T. To quantify geometric distortions, center of gravity analysis was carried out. Apparent diffusion coefficient (ADC) mapping in a diffusion phantom was performed to verify the diffusion sensitization within ms-RARE. An in vivo feasibility study in healthy volunteers (n = 10; mean age, 31 ± 7 years; mean body mass index, 22.6 ± 1.7 kg/m²) was conducted at 3.0 and 7.0 T to evaluate clinical feasibility of ms-RARE. As a precursor to a broader clinical study, patients (n = 6; mean age, 55 ± 12 years; mean body mass index, 27.5 ± 4.7 kg/m²) with an uveal melanoma and/or retinal detachment were examined at 3.0 and 7.0 T. In 1 case, the diseased eye was enucleated as part of the therapy and imaged afterward with magnetic resonance microscopy at 9.4 T. Macrophotography and histological investigation was carried out. For qualitative assessment of the image distortion, 3 independent readers reviewed and scored ms-RARE in vivo images for all subjects in a blinded reading session. Statistical significance in the difference of the scores (a) obtained for the pooled ms-RARE data with b = 0 and 300 s/mm² and (b) for the 3 readers was analyzed using the nonparametric Mann-Whitney test.
  
  
  RESULTS
  The assessment of geometric integrity in phantom imaging revealed the ability of ms-RARE to produce distortion-free images. Unlike ms-RARE, modest displacements (2.3 ± 1.4 pixels) from the fast low angle shot imaging reference were observed for readout-segmented EPI, which were aggravated for single-shot EPI (8.3 ± 5.7 pixels). These observations were confirmed in the in vivo feasibility study including distortion-free diffusion-weighted ophthalmic images with a 0.5 × 0.5 × 5 mm³ spatial resolution at 3.0 T and as good as 0.2 × 0.2 × 2 mm³ at 7.0 T. The latter represents a factor of 40 enhancement in spatial resolution versus clinical protocols recently reported for diffusion-weighted imaging of the eye at 1.5 T. Mean ADC values within the vitreous body were (2.91 ± 0.14) × 10⁻³ mm²/s at 3.0 T and (2.93 ± 0.41) × 10⁻³ mm²/s at 7.0 T. Patient data showed severe retinal detachment in the anatomical images. Whereas the tumor remained undetected in T1-weighted and T2-weighted imaging at 3.0/7.0 T, in vivo ADC mapping using ms-RARE revealed the presence of a uveal melanoma with a significant contrast versus the surrounding subretinal hemorrhage. This observation was confirmed by high-resolution ex vivo magnetic resonance microscopy and histology. Qualitative analysis of image distortion in ms-RARE images obtained for all subjects yielded a mean ± SD image quality score of 1.06 ± 0.25 for b = 0 s/mm² and of 1.17 ± 0.49 for b = 300 s/mm². No significant interreader differences were observed for ms-RARE with a diffusion sensitization of b = 0 s/mm² and 300 s/mm².
  
  
  CONCLUSIONS
  This work demonstrates the capability of diffusion-sensitized ms-RARE to acquire high-contrast, high-spatial resolution, distortion-free images of the eye and the orbit at 3.0 and 7.0 T. Geometric distortions that are observed for EPI-based imaging approaches even at lower field strengths are offset by fast spin-echo-based imaging techniques. The benefits of this improvement can be translated into the assessment of spatial arrangements of the eye segments and their masses with the ultimate goal to provide guidance during diagnostic treatment of ophthalmological diseases.
authors.affiliation: From the *Berlin Ultrahigh Field Facility (BUFF), Max-Delbrueck-Center for Molecular Medicine, Berlin; †MRI.TOOLS GmbH, Berlin; ‡Siemens Healthcare Sector, Erlangen; §Preclinical Imaging Research Group, University Medicine Rostock, Rostock; ∥Institute for Diagnostic Radiology and Neuroradiology, University of Greifswald, Greifswald; ¶Institute of Pathology, University Medicine Rostock, Rostock; #Department of Ophthalmology, University Medicine Rostock, Rostock; and **Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max-Delbrueck-Center for Molecular Medicine, Berlin, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Paul
authors.forename: Andreas
authors.initials: A
authors.lastname: Graessl
authors.forename: Jan
authors.initials: J
authors.lastname: Rieger
authors.forename: Darius
authors.initials: D
authors.lastname: Lysiak
authors.forename: Till
authors.initials: T
authors.lastname: Huelnhagen
authors.forename: Lukas
authors.initials: L
authors.lastname: Winter
authors.forename: Robin
authors.initials: R
authors.lastname: Heidemann
authors.forename: Tobias
authors.initials: T
authors.lastname: Lindner
authors.forename: Stefan
authors.initials: S
authors.lastname: Hadlich
authors.forename: Annette
authors.initials: A
authors.lastname: Zimpfer
authors.forename: Andreas
authors.initials: A
authors.lastname: Pohlmann
authors.forename: Beate
authors.initials: B
authors.lastname: Endemann
authors.forename: Paul-Christian
authors.initials: PC
authors.lastname: Krüger
authors.forename: Sönke
authors.initials: S
authors.lastname: Langner
authors.forename: Oliver
authors.initials: O
authors.lastname: Stachs
authors.forename: Thoralf
authors.initials: T
authors.lastname: Niendorf
mesh_terms: D016477:Artifacts; D003941:Diagnostic Techniques, Ophthalmological; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008545:Melanoma / Q000473:pathology*; D008875:Middle Aged; D009038:Motion; D010865:Pilot Projects; D012016:Reference Values; D015203:Reproducibility of Results; D012163:Retinal Detachment / Q000473:pathology*; D012680:Sensitivity and Specificity; D014604:Uveal Neoplasms / Q000473:pathology*; D000098943:Uveal Melanoma