T₁ Mapping From MPRAGE Acquisitions: Application to the Measurement of the Concentration of Nanoparticles in Tumors for Theranostic Use

Abstract

Background: The measurement of the concentration of theranostic agents in vivo is essential for the assessment of their therapeutic efficacy and their safety regarding healthy tissue. To this end, there is a need for quantitative T 1 measurements that can be obtained as part of a standard clinical imaging protocol applied to tumor patients. Purpose: To generate T 1 maps from MR images obtained with the magnetization-prepared rapid gradient echo (MPRAGE) sequence. To evaluate the feasibility of the proposed approach on phantoms, animal and patients with brain metastases. Study Type: Pilot. Phantom/Animal model/Population: Solutions containing contrast agents (chelated Gd 3+ and iron nanoparticles), male rat of Wistar strain, three patients with brain metastases. Field Strength/Sequence: A 3-T and 7-T, saturation recovery (SR), and MPRAGE sequences. Assessment: The MPRAGE T 1 measurement was compared to the reference SR method on phantoms and rat brain at 7-T. The robustness of the in vivo method was evaluated by studying the impact of misestimates of tissue proton density. Concentrations of Gd-based theranostic agents were measured at 3-T in gray matter and metastases in patients recruited in NanoRad clinical trial. Statistical Tests: A linear model was used to characterize the relation between T 1 measurements from the MPRAGE and the SR acquisitions obtained in vitro at 7-T. Results: The slope of the linear model was 0.966 (R 2 = 0.9934). MPRAGE-based T 1 values measured in the rat brain were 1723 msec in the thalamus. MPRAGE-based T 1 values measured in patients in white matter and gray matter amounted to 747 msec and 1690 msec. Mean concentration values of Gd 3+ in metastases were 61.47 μmol. Data Conclusion:The T 1 values obtained in vitro and in vivo support the validity of the proposed approach. The concentrations of Gd-based theranostic agents may be assessed in patients with metastases within a standard clinical imaging protocol using the MPRAGE sequence. Evidence Level: 2. Technical Efficacy: Stage 1.

Editorial for “T1Mapping From MPRAGE Acquisitions: Application to the Measurement of the Concentration of Nanoparticles in Tumors for Theranostic Use”

“…The results obtained from this study 7 are especially important in that they show that it is possible to estimate the concentration of contrast agents or theranostic agents of isotropic, high-resolution sequences such as the MPRAGE sequence, which is routinely used in the diagnosis and followup of central nervous system cancers. In addition, this study may also guide the sequences that can be used for the treatment and monitoring of cancers in other body regions (such as the abdomen, musculoskeletal) with therapeutic agents.…”

“…[1][2][3] In order to evaluate the efficacy of cancer treatments and their safety against healthy tissue, the tissue concentrations of the theraneustic agents used should be measured. For this purpose, the study of Lavielle et al 7 which argues that tissue concentrations of theraneustic agents on MRI can be derived from changes on T1 values induced on the assumption that longitudinal relaxivity r1 values are known, is published in this issue of the Journal of Magnetic Resonance Imaging. In this study, 7 although inversion recovery and saturation recovery (SR) sequences are considered the gold standard for creating T1 maps, these are not suitable for in vivo use due to their long acquisition times.…”

“…For this purpose, the study of Lavielle et al 7 which argues that tissue concentrations of theraneustic agents on MRI can be derived from changes on T1 values induced on the assumption that longitudinal relaxivity r1 values are known, is published in this issue of the Journal of Magnetic Resonance Imaging. In this study, 7 although inversion recovery and saturation recovery (SR) sequences are considered the gold standard for creating T1 maps, these are not suitable for in vivo use due to their long acquisition times. They suggested that instead of these sequences, magnetization prepared rapid gradient echo (MPRAGE) sequence can be used for this purpose in routine practice.…”

“…The MPRAGE sequence has become a part of the routine MRI protocol in many treatment and imaging units in the evaluation of tumoral processes before and after contrast agent administration, with isotropic high spatial resolution, strong T1‐weighted effect, and allowing rapid three‐dimensional imaging. In the study of Lavielle et al 7 the feasibility of T1 and contrast agent concentration maps obtained via MPRAGE were compared with gold standard SR gains in vitro and in vivo in animals and patients with brain metastases, with known T1 values in the brain. In this study, first, T1 maps were generated assuming the same proton densities and transverse relaxation time T2* values on the whole MPRAGE images.…”

“…In vitro validation of T1 measurements was performed on solutions containing ultra‐small nanoparticles (USNP) with maghemite iron oxide core of 4 ± 1 nm diameter coated with Gd‐based contrast agent and low molecular weight polyethylene glycol macromolecules. The clinical MPRAGE images used in the study 7 are from the NanoRad (Radiosensitization of Multiple Brain Metastases Using AGuIX Gadolinium‐Based Nanoparticles, NCT02820454) clinical trial, 8 completed in February 2019. As a result of this study, 7 they reported that the proposed approach and the algorithm used in this study were valid and robust in T1 measurements obtained in vitro on contrast agent solutions (Gadolinium‐based and USNP).…”