Probing lipids relaxation times in breast cancer using magnetic resonance spectroscopic fingerprinting.

OBJECTIVES: To investigate the clinical relevance of the relaxation times of lipids within breast cancer and normal fibroglandular tissue in vivo, using magnetic resonance spectroscopic fingerprinting (MRSF). METHODS: Twelve patients with biopsy-confirmed breast cancer and 14 healthy controls were prospectively scanned at 3 T using a protocol consisting of diffusion tensor imaging (DTI), MRSF, and dynamic contrast-enhanced (DCE) MRI. Single-voxel MRSF data was recorded from the tumor (patients) - identified using DTI - or normal fibroglandular tissue (controls), in under 20 s. MRSF data was analyzed using in-house software. Linear mixed model analysis was used to compare the relaxation times of lipids in breast cancer VOIs vs. normal fibroglandular tissue. RESULTS: Seven distinguished lipid metabolite peaks were identified and their relaxation times were recorded. Of them, several exhibited statistically significant changes between controls and patients, with strong significance (p < 10-3) recorded for several of the lipid resonances at 1.3 ppm (T1 = 355 ± 17 ms vs. 389 ± 27 ms), 4.1 ppm (T1 = 255 ± 86 ms vs. 127 ± 33 ms), 5.22 ppm (T1 = 724 ± 81 ms vs. 516 ± 62 ms), and 5.31 ppm (T2 = 56 ± 5 ms vs. 44 ± 3.5 ms, respectively). CONCLUSIONS: The application of MRSF to breast cancer imaging is feasible and achievable in clinically relevant scan time. Further studies are required to verify and comprehend the underling biological mechanism behind the differences in lipid relaxation times in cancer and normal fibroglandular tissue. KEY POINTS: •The relaxation times of lipids in breast tissue are potential markers for quantitative characterization of the normal fibroglandular tissue and cancer. •Lipid relaxation times can be acquired rapidly in a clinically relevant manner using a single-voxel technique, termed MRSF. •Relaxation times of T1 at 1.3 ppm, 4.1 ppm, and 5.22 ppm, as well as of T2 at 5.31 ppm, were significantly different between measurements within breast cancer and the normal fibroglandular tissue.

Selective excitation with recoupling pulse schemes uncover properties of disordered mineral phases in bone-like apatite grown with bone proteins.

Bone construction has been under intensive scrutiny for many years using numerous techniques. Solid-state NMR spectroscopy helped unravel key characteristics of the mineral structure in bone owing to its capability of analyzing crystalline and disordered phases at high-resolution. This has invoked new questions regarding the roles of persistent disordered phases in structural integrity and mechanical function of mature bone as well as regarding regulation of early events in formation of apatite by bone proteins which interact intimately with the different mineral phases to exert biological control. Here, spectral editing tethered to standard NMR techniques is employed to analyze bone-like apatite minerals prepared synthetically in the presence and absence of two non-collagenous bone proteins, osteocalcin and osteonectin. A 1H spectral editing block allows excitation of species from the crystalline and disordered phases selectively, facilitating analysis of phosphate or carbon species in each phase by magnetization transfer via cross polarization. Further characterization of phosphate proximities using SEDRA dipolar recoupling, cross-phase magnetization transfer using DARR and T1/T2 relaxation times demonstrate that the mineral phases formed in the presence of bone proteins are more complex than bimodal. They reveal disparities in the physical properties of the mineral layers, indicate the layers in which the proteins reside and highlight the effect that each protein imparts across the mineral layers.

What is the optimal schedule for multiparametric MRS? A magnetic resonance fingerprinting perspective.

Clinical magnetic resonance spectroscopy (MRS) mainly concerns itself with the quantification of metabolite concentrations. Metabolite relaxation values, which reflect the microscopic state of specific cellular and sub-cellular environments, could potentially hold additional valuable information, but are rarely acquired within clinical scan times. By varying the flip angle, repetition time and echo time in a preset way (termed a schedule), and matching the resulting signals to a pre-generated dictionary - an approach dubbed magnetic resonance fingerprinting - it is possible to encode the spins' relaxation times into the acquired signal, simultaneously quantifying multiple tissue parameters for each metabolite. Herein, we optimized the schedule to minimize the averaged root mean square error (RMSE) across all estimated parameters: concentrations, longitudinal and transverse relaxation time, and transmitter inhomogeneity. The optimal schedules were validated in phantoms and, subsequently, in a cohort of healthy volunteers, in a 4.5 mL parietal white matter single voxel and an acquisition time under 5 minutes. The average intra-subject, inter-scan coefficients of variation (CVs) for metabolite concentrations, T1 and T2 relaxation times were found to be 3.4%, 4.6% and 4.7% in-vivo, respectively, averaged over all major singlets. Coupled metabolites were quantified using the short echo time schedule entries and spectral fitting, and reliable estimates of glutamate+glutamine, glutathione and myo-inositol were obtained.

How does osteocalcin lacking γ-glutamic groups affect biomimetic apatite formation and what can we say about its structure in mineral-bound form?

Non-collagenous proteins such as osteocalcin function as regulators of the mineralization process in bone. Osteocalcin undergoes post-translational modification adding an extra carboxylate group on three of its glutamate residues to enhance interaction with bone mineral. In this work, we examine regulation of biomimetic apatite formation by osteocalcin that was not modified after translation. We analyze the structural features in the protein and mineral-protein interfaces to elicit the unmodified protein's fold inside the mineral and to unveil the species that interact with the mineral surface. The results presented here give clues on the protein's active role in controlling the mineral phases that are formed on hydroxyapatite crystals and its ability to influence the extent of order in these crystals.

The application of magnetic resonance fingerprinting to single voxel proton spectroscopy.

Magnetic resonance fingerprinting has been proposed as a method for undersampling k-space while simultaneously yielding multiparametric tissue maps. In the context of single voxel spectroscopy, fingerprinting can provide a unified framework for parameter estimation. We demonstrate the utility of such a magnetic resonance spectroscopic fingerprinting (MRSF) framework for simultaneously quantifying metabolite concentrations, T1 and T2 relaxation times and transmit inhomogeneity for major singlets of N-acetylaspartate, creatine and choline. This is achieved by varying TR , TE and the flip angle of the first pulse in a PRESS sequence between successive excitations (i.e. successive TR values). The need for multiparametric schemes such as MRSF for accurate medical diagnostics is demonstrated with the aid of realistic in vivo simulations; these show that certain schemes lead to substantial increases to the area under receiver operating characteristics of metabolite concentrations, when viewed as classifiers of pathologies. Numerical simulations and phantom and in vivo experiments using several different schedules of variable length demonstrate superior precision and accuracy for metabolite concentrations and longitudinal relaxation, and similar performance for the quantification of transverse relaxation.