This study explored the usefulness of multiple quantitative MRI approaches to detect pancreatic ductal adenocarcinomas in two murine models, PAN-02 and KPC. Methods assayed included 1 H T 1 and T 2 measurements, quantitative diffusivity mapping, magnetization transfer (MT) 1 H MRI throughout the abdomen and hyperpolarized 13 C spectroscopic imaging. The progress of the disease was followed as a function of its development; studies were also conducted for wildtype control mice and for mice with induced mild acute pancreatitis. Customized methods developed for scanning the motion-and artifact-prone mice abdomens allowed us to obtain quality 1 H images for these targeted regions. Contrasts between tumors and surrounding tissues, however, were significantly different. Anatomical images, T 2 maps and MT did not yield significant contrast unless tumors were large. By contrast, tumors showed statistically lower diffusivities than their surroundings (≈8.3 ± 0.4 x 10 −4 for PAN-02 and ≈10.2 ± 0.6 x 10 −4 for KPC vs 13 ± 1 x 10 −3 mm 2 s −1 for surroundings), longer T 1 relaxation times (≈1.44 ± 0.05 for PAN-02 and ≈1.45 ± 0.05 for KPC vs 0.95 ± 0.10 seconds for surroundings) and significantly higher lactate/ pyruvate ratios by hyperpolarized 13 C MR (0.53 ± 0.2 for PAN-02 and 0.78 ± 0.2 for KPC vs 0.11 ± 0.04 for control and 0.31 ± 0.04 for pancreatitis-bearing mice). Although the latter could also distinguish early-stage tumors from healthy animal controls, their response was similar to that in our pancreatitis model. Still, this ambiguity could be lifted using the 1 H-based reporters. If confirmed for other kinds of pancreatic tumors this means that these approaches, combined, can provide a route to an early detection of pancreatic cancer.
Deuterium metabolic imaging (DMI) is a promising molecular MRI approach, which follows the administration of deuterated substrates and their metabolization. [6,6’‐2H2]‐glucose for instance is preferentially converted in tumors to [3,3’‐2H2]‐lactate as a result of the Warburg effect, providing a distinct resonance whose mapping using time‐resolved spectroscopic imaging can diagnose cancer. The MR detection of low‐concentration metabolites such as lactate, however, is challenging. It has been recently shown that multi‐echo balanced steady‐state free precession (ME‐bSSFP) increases the signal‐to‐noise ratio (SNR) of these experiments approximately threefold over regular chemical shift imaging; the present study examines how DMI's sensitivity can be increased further by advanced processing methods. Some of these, such as compressed sensing multiplicative denoising and block‐matching/3D filtering, can be applied to any spectroscopic/imaging methods. Sensitivity‐enhancing approaches were also specifically tailored to ME‐bSSFP DMI, by relying on priors related to the resonances' positions and to features of the metabolic kinetics. Two new methods are thus proposed that use these constraints for enhancing the sensitivity of both the spectral images and the metabolic kinetics. The ability of these methods to improve DMI is evidenced in pancreatic cancer studies carried at 15.2 T, where suitable implementations of the proposals imparted eightfold or more SNR improvement over the original ME‐bSSFP data, at no informational cost. Comparisons with other propositions in the literature are briefly discussed.
Purpose:To develop a pulse sequence for acquiring robust, quantitative T 2 relaxation maps in real time. Methods: The pulse scheme relies on fully refocused spatiotemporally encoded multi-spin-echo trains, which provide images that are significantly less distorted than spin-echo echo planar imaging-based counterparts. This enables single-shot T 2 mapping in inhomogeneity-prone regions. Another advantage of these schemes stems from their ability to interleave multiple scans in a reference-free manner, providing an option to increase sensitivity and spatial resolution with minimal motional artifacts. Results: The method was implemented in preclinical and clinical scanners, where single-shot acquisitions delivered reliable T 2 maps in ≤200 ms with ≈250 µm and ≈3 mm resolutions, respectively. Ca. 4 times higher spatial resolutions were achieved for the motion-compensated interleaved versions of these acquisitions, delivering T 2 maps in ca. 10 s per slice. These maps were nearly indistinguishable from multiscan relaxometric maps requiring orders-of-magnitude longer acquisitions; this was confirmed by mice head and real-time mice abdomen 7T scans performed following contrast-agent injections, as well as by 3T human brain and breast scans. Conclusion: This study introduced and demonstrated a new approach for acquiring rapid and quantitative T 2 data, which is particularly reliable when operating at high fields and/or targeting heterogeneous organs or regions. K E Y W O R D Sabdominal imaging, breast MRI, multi-spin-echo sequences, quantitative T2 mapping, spatiotemporal encoding
Chemical exchange saturation transfer (CEST) experiments enhance the NMR signals of labile protons by continuously transferring these protons' saturation to an abundant solvent pool like water. The present study expands these principles by fusing into these experiments homonuclear isotropic mixing sequences, enabling the water-enhanced detection of non-exchangeable species. Further opportunities are opened by the addition of coupling-mediated heteronuclear polarization transfers, which then impose on the water resonance a saturation stemming from non-labile heteronuclear species like C. To multiplex the ensuing experiments, these relayed approaches are combined with time-domain schemes involving multiple Ramsey-labeling experiments imparting the frequencies of the non-labile sites on the water resonance, via chemical exchange.C and H NMR spectra were detected in this fashion with about two-fold SNR amplification vis-à-vis conventionally detected spectroscopies. When combined with non-uniform sampling principles, this methodology thus becomes a sensitive alternative to detect non-exchangeable species in biomolecules. Still, multiple parameters including the scalar couplings and solvent exchange rates, will affect the efficiency and consequently the practicality of the overall experiment.
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