Method Development RR Example

Example Registered Report Abstract - Method Development

Title

Fast B1-Insensitive Mapping of T1 Relaxation Times in the Brain: A Registered Report

Introduction

Accurate quantification of T1 relaxation times in brain tissue is crucial for detecting subtle pathological changes and for longitudinal assessment of disease progression. Current T1 mapping techniques suffer from various limitations including sensitivity to B1 inhomogeneities, long acquisition times, or limited precision in specific tissue types. We propose a novel approach (FastT1) that addresses these limitations by combining undersampled radial acquisitions with a tissue-specific signal model. This registered report outlines our validation plan to evaluate the accuracy, precision, and clinical utility of FastT1 compared to established methods.

Theory and methods

FastT1 uses a specific RF pulse scheme in a radial gradient echo acquisition to sensitize the readout to multiple T1 values.

Hypothesis

We hypothesize that FastT1 will provide T1 measurements with (1) equivalent or superior accuracy (< 3% deviation from reference standards) compared to the current gold standard (inversion recovery spin echo), (2) improved precision (< 5% coefficient of variation) in white matter structures, and (3) reduced acquisition time (< 3 minutes for whole-brain coverage), while maintaining robustness to B1 inhomogeneities (< 2% error for B1 variations of ±20%).

Preliminary Data

Initial phantom experiments (n=8 T1 values ranging from 300-2000ms) demonstrate a strong correlation between our method and reference standards (r=0.98, p<0.001) with mean difference of 2.1% across the T1 range. Preliminary in vivo testing in healthy volunteers (n=5) shows consistent T1 measurements across repeated scans (coefficient of variation: 3.8% in white matter, 4.2% in gray matter) and minimal sensitivity to simulated B1 variations (1.8% change in T1 with ±15% B1 variation). Whole-brain coverage was achieved in 2:47 minutes.

Study protocol

Study Design

We will conduct a two-part validation study: (1) comprehensive phantom validation and (2) in vivo validation in healthy volunteers (n=20) and patients with multiple sclerosis (n=15).

MR Acquisition

All scans will be performed on a 3T MRI system (Manufacturer, Model) with a 32-channel head coil. The protocol will include:

• FastT1 acquisition (prototype sequence)
• Inversion recovery spin echo (IRSE) as reference standard
• Variable flip angle (VFA) method
• MP2RAGE sequence

Each subject will be scanned twice within a 7-day interval to assess reproducibility.

Analysis Approach

T1 maps will be generated using method-specific reconstruction algorithms. ROI analysis will be performed in standardized brain regions (frontal WM, occipital WM, thalamus, putamen, cortical GM). For MS patients, additional ROI analysis will include lesions and normal-appearing white matter. Bland-Altman analysis will assess agreement between methods.

Statistical Analysis Plan

Primary Outcomes

1. Accuracy: Mean percentage difference between FastT1 and IRSE measurements
2. Precision: Coefficient of variation between repeated measurements
3. B1 sensitivity: Percentage change in T1 with simulated B1 variations

Sample Size Justification

Based on our preliminary data (mean difference of 2.1%, SD=1.2%), a sample of 20 healthy volunteers will provide 95% power to detect a 3% difference from the reference standard (α=0.05). For MS patients, 15 subjects will allow detection of a 5% difference in T1 values between normal-appearing white matter and lesions (α=0.05, power=90%).

Statistical Tests

• Paired t-tests for method comparisons
• Intraclass correlation coefficients for reproducibility
• ANOVA for effects of B1 variation on T1 measurements
• Linear regression to assess agreement with reference standards