Abstract
Abstract Introduction Difficulties with arousal and orgasm are common in female patients after pelvic radiation. Yet, current classifications of toxicity and normal tissues in radiation oncology account poorly for the anatomy and critical function of female erectile tissues (arousal and orgasm) with respect to patients’ capacities to continue to engage in pleasurable sexual behaviors after cancer treatment. MRI imaging biomarkers of dose-volume dependent radiation damage can provide objective measures of the impact of interventions, help predict sexual dysfunction, and allow for re-optimization of therapy for early mitigation of radiation damage to female erectile tissues. Objective The aim of this project is to develop and optimize MRI imaging techniques for female erectile tissues and other genitopelvic organs. Optimization of this MRI protocol will allow us to establish quantitative and qualitative indices of radiation damage to specific sexual organs, providing mechanistic insights into how to measure radiation damage of current and future therapies. Methods This prospective study includes two female-identifying volunteers with healthy female pelvic anatomy who underwent MRI scans using a 3.0T MRI (Prisma, Siemens Healthcare) scanner. The protocol (Table 1) included 2D T2-weighted turbo spin-echo (TSE) sequences in the axial (spatial resolution 0.5x0.5x2mm), coronal (spatial resolution 0.5x0.5x3mm), and sagittal planes (spatial resolution 0.3x0.3x2mm), T2-weighted with fat saturation in the axial plane (spatial resolution: 0.8x0.8x4mm) diffusion-weighted tensor imaging (DTI, axial plane with 30 diffusion directions and b-values 0s/mm2 and 400s/mm2, TR/TE: 3000/57ms, spatial resolution 1.3x1.3x5mm). Protocol optimization in healthy volunteers consisted of imaging without gadolinium contrast, while future imaging in patients will also include dynamic contrast-enhanced MRI (3D T1-weighted radial acquisition in the axial plane, with 4.7s temporal resolution, 20 slices, spatial resolution 0.8x0.8x2mm) and T1 mapping (axial plane variable flip angle, B1-corrected acquisition with 5 flip angles: 5, 10, 15, 20, 30 degrees, TR/TE: 5.9/2.4ms, with 0.8x0.8x2mm spatial resolution). The sexual regions of interest (ROIs) included the female external genitalia, vagina, bulboclitoris (clitoris and vestibular bulbs), pelvic neurovasculature, and pelvic floor muscles which were visualized and contoured per standard protocols. Results The axial T2-weighted TSE sequences in 2mm slices provided clear visualization of the female erectile tissues for contouring the bulboclitoris, vaginal canal, and external genitalia (Figure 1). The T2-weighted sequences with fat saturation allows us to conduct MR neurography to evaluate the three-dimensional visibility of the nerves (plexus, pudendal and cavernous), enabling us to localize and characterize nerve abnormalities with dose-dependent radiation damage (Figure 2). Perfusion time intensity curves created with the T1 DCE scans can assess changes in vasculature, and the initial areas under the time to signal intensity curve (IAUC) will act as biomarkers for erectile tissue perfusion and permeability. Additional biomarkers include ROI intensity and volume/thickness for both erectile tissues and the vagina wall, as well as fractional anisotropy for the vagina alone. Lastly, we explore the clinical applications of DTI with fiber tractography to evaluate pelvic floor musculature. Conclusions These MRI techniques will be the first to validate normal tissue toxicity imaging biomarkers for radiation damage, allowing us to objectively measure dose-dependent inflammatory, fibrotic and vasculogenic effects of radiotherapy. Disclosure No.
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