Magnetization transfer MRI of 3rd trimester fetal brain: A pilot of gestational myelin imaging

Siddharth Sadanand ¹ Rob Stobbe ² Tim van Mieghem ^3,4 Pradeep Krishnan ⁵ Shiri Shinar ³ Greg Jan Stanisz ^4,6 Dafna Sussman ^1,4*

• ¹ Toronto Metropolitan University, Toronto, Canada
• ² University of Alberta, Edmonton, Alberta, Canada
• ³ Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
• ⁴ University of Toronto, Toronto, Ontario, Canada
• ⁵ SickKids Foundation, Toronto, Ontario, Canada
• ⁶ Sunnybrook Research Institute (SRI), Toronto, Ontario, Canada

Background: Magnetic Resonance Imaging (MRI) is commonly used to confirm a fetal brain abnormality suspected on ultrasound. Common clinical MRI sequences typically reveal changes in the brain only once gross abnormalities appear. Detecting more minute changes in brain tissue microstructure could permit earlier detection of complications, allowing for more timely, effective interventions. Tissue microstructure corresponding to neuronal development can be captured before broad anatomical changes appear using advanced imaging, such as magnetization transfer (MT) MRI. This study aimed to investigate the feasibility of an MT MRI pulse sequence, YB MT, for fetal brain imaging.Methods: A yarnball (YB) readout trajectory accelerated imaging and increased sensitivity. A multiband saturation pulse increased MT-specificity from saturation transfer (ST) confounds. MT-weighted images were derived from 3-point magnetization transfer ratio asymmetry (MTRasym) to reduce acquisition time to a breath hold. Sensitivity and specificity were evaluated on agar phantoms with varied MT and ST confound concentrations. Pilot imaging was done with singleton 3rd trimester gestations complicated with mild ventriculomegaly recruited from Mount Sinai Hospital.Results: YB MT covers a 350 mm 3D field of view (FoV) within a 13 s breath hold and a 28 s acquisition. The sequence demonstrated a limit of quantification (LOQ) of agar of 0.62%w/w and no dependence on glucose in agar phantoms with glucose ST confound. Pilot imaging in vivo of 3rd trimester pregnancies with mild ventriculomegaly revealed MT contrast in the fetal brain spatially consistent with white matter development at this gestational age. All participants reported the sequence and breath hold to be tolerable.Conclusion: The developed YB MT pulse sequence is sensitive to fetal physiological MT signal, tolerable to participants, and does not demonstrate sensitivity to ST confounds in phantom imaging. While the breath hold was reported tolerable, motion artefacts and spiral trajectory blurring affected subjects’ imaging. Ongoing work, including online reconstruction, expedited trajectories, and improved signal-to-noise ratio, should address these challenges. This proof-of-principle is a step toward clinical translation of gestational metabolic imaging, such as MT imaging of fetal myelin, for early detection of gestational complications.