High efficacy of CD19 CAR T cells in patients with transformed Waldenström macroglobulinemia.

ABSTRACT: Histologic transformation of Waldenström macroglobulinemia (HT-WM) carries a poor prognosis with standard treatments. Here, we report the first series of HT-WM treated with chimeric antigen receptor T cells showing a high efficacy and no unexpected toxicity.

Accumulation of Lithium in the Hippocampus of Patients With Bipolar Disorder: A Lithium-7 Magnetic Resonance Imaging Study at 7 Tesla.

BACKGROUND: Lithium (Li) is a first-line treatment for bipolar disorder (BD). To study its cerebral distribution and association with plasma concentrations, we used 7Li magnetic resonance imaging at 7T in euthymic patients with BD treated with Li carbonate for at least 2 years. METHODS: Three-dimensional 7Li magnetic resonance imaging scans (N = 21) were acquired with an ultra-short echo-time sequence using a non-Cartesian k-space sampling scheme. Lithium concentrations ([Li]) were estimated using a phantom replacement approach accounting for differential T1 and T2 relaxation effects. In addition to the determination of mean regional [Li] from 7 broad anatomical areas, voxel- and parcellation-based group analyses were conducted for the first time for 7Li magnetic resonance imaging. RESULTS: Using unprecedented spatial sensitivity and specificity, we were able to confirm the heterogeneity of the brain Li distribution and its interindividual variability, as well as the strong correlation between plasma and average brain [Li] ([Li]B ≈ 0.40 × [Li]P, R = .74). Remarkably, our statistical analysis led to the identification of a well-defined and significant cluster corresponding closely to the left hippocampus for which high Li content was displayed consistently across our cohort. CONCLUSIONS: This observation could be of interest considering 1) the major role of the hippocampus in emotion processing and regulation, 2) the consistent atrophy of the hippocampus in untreated patients with BD, and 3) the normalization effect of Li on gray matter volumes. This study paves the way for the elucidation of the relationship between Li cerebral distribution and its therapeutic response, notably in newly diagnosed patients with BD.

Tissue sodium concentration and sodium T1 mapping of the human brain at 3 T using a Variable Flip Angle method.

PURPOSE: The state-of-the-art method to quantify sodium concentrations in vivo consists in a fully relaxed 3D spin-density (SD) weighted acquisition. Nevertheless, most sodium MRI clinical studies use short-TR SD acquisitions to reduce acquisition durations. We present a clinically viable implementation of the Variable Flip Angle (VFA) method for robust and clinically viable quantification of total sodium concentration (TSC) and longitudinal relaxation rates in vivo in human brain at 3 T. METHODS: Two non-Cartesian steady-state spoiled ultrashort echo time (UTE) scans, performed at optimized flip angles, repetition time and pulse length determined under specific absorption rate constraints, are used to simultaneously compute T1 and total sodium concentration (TSC) maps using the VFA method. Images are reconstructed using the non-uniform Fast Fourier Transform algorithm and TSC maps are corrected for possible inhomogeneity of coil transmission and reception profiles. Fractioned acquisitions are used to correct for potential patient motion. TSC quantifications obtained using the VFA method are validated at first in comparison with a fully-relaxed SD acquisition in a calibration phantom. The robustness of similar VFA acquisitions are compared to the short-TR SD approach in vivo on seven healthy volunteers. RESULTS: The VFA method resulted in consistent TSC and T1 estimates across our cohort of healthy subjects, with mean TSC of 38.1 ±â€¯5.0 mmol/L and T1 of 39.2 ±â€¯4.4 ms. These results are in agreement with previously reported values in literature TSC estimations and with the predictions of a 2-compartment model. However, the short-TR SD acquisition systematically underestimated the sodium concentration with a mean TSC of 31 ±â€¯4.5 mmol/L. CONCLUSION: The VFA method can be applied successfully to image sodium at 3 T in about 20 min and provides robust and intrinsically T1-corrected TSC maps.

Simultaneous multi-parametric mapping of total sodium concentration, T1, T2 and ADC at 7 T using a multi-contrast unbalanced SSFP.

PURPOSE: Quantifying multiple NMR properties of sodium could be of benefit to assess changes in cellular viability in biological tissues. A proof of concept of Quantitative Imaging using Configuration States (QuICS) based on a SSFP sequence with multiple contrasts was implemented to extract simultaneously 3D maps of applied flip angle (FA), total sodium concentration, T1, T2, and Apparent Diffusion Coefficient (ADC). METHODS: A 3D Cartesian Gradient Recalled Echo (GRE) sequence was used to acquire 11 non-balanced SSFP contrasts at a 6 × 6 × 6 mm3 isotropic resolution with carefully-chosen gradient spoiling area, RF amplitude and phase cycling, with TR/TE = 20/3.2 ms and 25 averages, leading to a total acquisition time of 1 h 18 min. A least-squares fit between the measured and the analytical complex signals was performed to extract quantitative maps from a mono-exponential model. Multiple sodium phantoms with different compositions were studied to validate the ability of the method to measure sodium NMR properties in various conditions. RESULTS: Flip angle maps were retrieved. Relaxation times, ADC and sodium concentrations were estimated with controlled precision below 15%, and were in accordance with measurements from established methods and literature. CONCLUSION: The results illustrate the ability to retrieve sodium NMR properties maps, which is a first step toward the estimation of FA, T1, T2, concentration and ADC of 23Na for clinical research. With further optimization of the acquired QuICS contrasts, scan time could be reduced to be suitable with in vivo applications.