The Fusion of MRI and CT in the Planning of Brachytherapy for Cancer of the Uterine Cervix

Introduction: tumors of the uterine cervix are among the most common carcinomas in women. Intracervical brachytherapy is an indispensable part of curative treatment. Although the tumor is significantly more recognizable in MRI than in CT, the practical application of MRI in brachytherapy planning is still difficult. The present study examines the technical possibilities of merging CT and MRI. Materials and Methods: the treatment files and imaging of all 53 patients who had been irradiated by image-guided adaptive brachytherapy (IGABT) between January 2019 and August 2021 at the Department of Radiotherapy of the Hannover Medical School were evaluated, retrospectively. Patients were treated first with an external beam radiotherapy (EBRT) combined with simultaneous chemotherapy. After an average of 4.2 weeks, the preparation for IGABT began. The clinical target volume (CTV) for brachytherapy was contoured first in an MRI acquired before starting EBRT (MRI 1) and once more in a second MRI just before starting IGABT (MRI 2). Then, after inserting the intravaginal applicator, a CT-scan was acquired, and the CTV was contoured in the CT. Finally, the recordings of MRI 1, MRI 2, and the CT were merged, and the congruence of CTVs was quantitatively evaluated. Results: the CTV delineated in MRI 2 was, on average, 28% smaller than that in MRI 1 after an average applied radiation dose of 42 Gy. The CTV delineated in the CT covered an average of no more than 80.8% of the CTV delineated in MRI 2. The congruence of CTVs was not superior in patients with a smit sleeve in the cervical channel, with a 3D-volumetric MRI or with a contrast-enhanced sequence for MRI. Conclusion: the anatomical shape and position of the uterus is significantly changed by introducing a vaginal applicator. Despite the superior delimitability of the tumor in MRI, brachytherapy cannot be reliably planned by the image fusion of an MRI without a vaginal applicator.

Volumetric MRI is a promising outcome measure of muscle reinnervation

The development of outcome measures that can track the recovery of reinnervated muscle would benefit the clinical investigation of new therapies which hope to enhance peripheral nerve repair. The primary objective of this study was to assess the validity of volumetric Magnetic Resonance Imaging (MRI) as an outcome measure of muscle reinnervation by testing its reproducibility, responsiveness and relationship with clinical indices of muscular function. Over a 3-year period 25 patients who underwent nerve transfer to reinnervate elbow flexor muscles were assessed using intramuscular electromyography (EMG) and MRI (median post-operative assessment time of 258 days, ranging from 86 days pre-operatively to 1698 days post- operatively). Muscle power (Medical Research Council (MRC) grade) and Stanmore Percentage of Normal Elbow Assessment (SPONEA) assessment was also recorded for all patients. Sub-analysis of peak volitional force (PVF), muscular fatigue and co-contraction was performed in those patients with MRC > 3. The responsiveness of each parameter was compared using Pearson or Spearman correlation. A Hierarchical Gaussian Process (HGP) was implemented to determine the ability of volumetric MRI measurements to predict the recovery of muscular function. Reinnervated muscle volume per unit Body Mass Index (BMI) demonstrated good responsiveness (R2 = 0.73, p < 0.001). Using the temporal and muscle volume per unit BMI data, a HGP model was able to predict MRC grade and SPONEA with a mean absolute error (MAE) of 0.73 and 1.7 respectively. Muscle volume per unit BMI demonstrated moderate to good positive correlations with patient reported impairments of reinnervated muscle; co- contraction (R2 = 0.63, p = 0.02) and muscle fatigue (R2 = 0.64, p = 0.04). In summary, volumetric MRI analysis of reinnervated muscle is highly reproducible, responsive to post-operative time and demonstrates correlation with clinical indices of muscle function. This encourages the view that volumetric MRI is a promising outcome measure for muscle reinnervation which will drive advancements in motor recovery therapy.

Recommendations to Optimize the Use of Volumetric MRI in Huntington's Disease Clinical Trials

Volumetric magnetic resonance imaging (vMRI) has been widely studied in Huntington's disease (HD) and is commonly used to assess treatment effects on brain atrophy in interventional trials. Global and regional trajectories of brain atrophy in HD, with early involvement of striatal regions, are becoming increasingly understood. However, there remains heterogeneity in the methods used and a lack of widely-accessible multisite, longitudinal, normative datasets in HD. Consensus for standardized practices for data acquisition, analysis, sharing, and reporting will strengthen the interpretation of vMRI results and facilitate their adoption as part of a pathobiological disease staging system. The Huntington's Disease Regulatory Science Consortium (HD-RSC) currently comprises 37 member organizations and is dedicated to building a regulatory science strategy to expedite the approval of HD therapeutics. Here, we propose four recommendations to address vMRI standardization in HD research: (1) a checklist of standardized practices for the use of vMRI in clinical research and for reporting results; (2) targeted research projects to evaluate advanced vMRI methodologies in HD; (3) the definition of standard MRI-based anatomical boundaries for key brain structures in HD, plus the creation of a standard reference dataset to benchmark vMRI data analysis methods; and (4) broad access to raw images and derived data from both observational studies and interventional trials, coded to protect participant identity. In concert, these recommendations will enable a better understanding of disease progression and increase confidence in the use of vMRI for drug development.

Serum NfL in spinocerebellar ataxia type 1 is increased already at the preataxic stage, correlating with proximity to clinical onset

Background and Objectives. Neurofilament light (NfL) appears a promising fluid biomarker in repeat-expansion spinocerebellar ataxias (SCAs), with piloting studies in mixed SCA cohorts suggesting that NfL might be increased at the ataxic stage of spinocerebellar ataxia type 1 (SCA1). We here hypothesised that NfL is increased not only at the ataxic stage of SCA1, but also at its - likely most treatment-relevant - preataxic stage. Methods. We assessed serum (sNfL) and cerebrospinal fluid (cNfL) levels of NfL in both preataxic and ataxic SCA1, leveraging a multicentric cohort of 40 SCA1 carriers (23 preataxic, 17 ataxic) and >80 controls, and clinical follow-up data including actually observed (rather than only predicted) conversion to the ataxic stage (11 carriers). Results. sNfL levels were increased with high age-corrected effect sizes at the preataxic (r=0.62) and ataxic stage (r=0.63), paralleling increases of cNfL levels. In preataxic subjects, sNfL levels increased with proximity to predicted ataxia onset, with significant sNfL elevations already 5 years before onset, and confirmed in preataxic subjects with actually observed ataxia onset. sNfL increases were detected already in preataxic SCA1 subjects without volumetric atrophy of cerebellum or pons, suggesting that sNfL might be more sensitive to early preataxic neurodegeneration than the currently known most change-sensitive regions in volumetric MRI. Using longitudinal sNfL measurements, we estimated sample sizes for clinical trials using the reduction of sNfL as endpoint. Conclusions. sNfL levels might thus provide easily accessible peripheral biomarkers in both preataxic and ataxic SCA1, allowing stratification of preataxic subjects regarding proximity-to-onset, early detection of neurodegeneration even before volumetric MRI alterations, and potentially capture of treatment response in clinical trials.