Phosphorus (31P) MRSI provides opportunities to monitor potential biomarkers. However, current applications of 31P MRS are generally restricted to relatively small volumes as small coils are used. Conventional surface coils require high energy adiabatic RF pulses to achieve flip angle homogeneity, leading to high specific absorption rates (SARs), and occupy space within the MRI bore. A birdcage coil behind the bore cover can potentially reduce the SAR constraints massively by use of conventional amplitude modulated pulses without sacrificing patient space. Here, we demonstrate that the integrated 31P birdcage coil setup with a high power RF amplifier at 7 T allows for low flip angle excitations with short repetition time (T R) for fast 3D chemical shift imaging (CSI) and 3D T 1‐weighted CSI as well as high flip angle multi‐refocusing pulses, enabling multi‐echo CSI that can measure metabolite T 2, over a large field of view in the body. B 1 + calibration showed a variation of only 30% in maximum B 1 in four volunteers. High signal‐to‐noise ratio (SNR) MRSI was obtained in the gluteal muscle using two fast in vivo 3D spectroscopic imaging protocols, with low and high flip angles, and with multi‐echo MRSI without exceeding SAR levels. In addition, full liver MRSI was achieved within SAR constraints. The integrated 31P body coil allowed for fast spectroscopic imaging and successful implementation of the multi‐echo method in the body at 7 T. Moreover, no additional enclosing hardware was needed for 31P excitation, paving the way to include larger subjects and more space for receiver arrays. The increase in possible number of RF excitations per scan time, due to the improved B 1 + homogeneity and low SAR, allows SNR to be exchanged for spatial resolution in CSI and/or T 1 weighting by simply manipulating T R and/or flip angle to detect and quantify ratios from different molecular species.
Currently, it is difficult to predict effective therapy response to molecular therapies for the treatment of lung cancer based solely on anatomical images. 31 P MR spectroscopic imaging could provide as a non-invasive method to monitor potential biomarkers for early therapy evaluation, a necessity to improve personalized care and reduce cost. However, surface coils limit the imaging volume in conventional 31 P MRSI. High-energetic adiabatic RF pulses are required to achieve flip angle homogeneity but lead to high SAR. Birdcage coils permit use of conventional amplitude modulated pulses, even over large FOV, potentially decreasing overall SAR massively.Here, we investigate the feasibility of 3D 31 P MRSI at 7 T in lung carcinoma patients using an integrated 31 P birdcage body coil in combination with either a dual-coil or a 16-channel receiver.Simulations showed a maximum decrease in SNR per unit of time of 8% for flip angle deviations in short TR low flip-angle excitation 3D CSI. The minimal SNR loss allowed for fast 3D CSI without time-consuming calibration steps (>10:00 min.). 31 P spectra from four lung carcinoma patients were acquired within 29:00 minutes and with high SNR using both receivers. The latter allowed discrimination of individual phosphodiesters, inorganic phosphate, phosphocreatine and ATP. The receiver array allowed for an increased FOV compared to the dual-coil receiver.3D 31 P-CSI were acquired successfully in four lung carcinoma patients using the integrated 31 P body coil at ultra-high field. The increased spectral resolution at 7 T allowed differentiation of multiple 31 P metabolites related to phospholipid and energy metabolism. Simulations provide motivation to exclude 31 P B 1 calibrations, potentially decreasing total scan duration. Employing large receiver arrays improves the field of view allowing for full organ coverage. 31 P MRSI is feasible in lung carcinoma patients
In solid tumors, rapid local intravascular release of anticancer agents, e.g., doxorubicin (DOX), from thermosensitive liposomes (TSLs) can be an option to overcome poor extravasation of drug nanocarriers. The driving force of DOX penetration is the drug concentration gradient between the vascular compartment and the tumor interstitium. In this feasibility study, we used fibered confocal fluorescence microscopy (FCFM) to monitor in real-time DOX penetration in the interstitium of a subcutaneous tumor after its intravascular release from TSLs, Thermodox®. Cell uptake kinetics of the released DOX was quantified, along with an in-depth assessment of released-DOX penetration using an evolution model. A subcutaneous rat R1 rhabdomyosarcoma xenograft was used. The rodent was positioned in a setup including a water bath, and FCFM identification of functional vessels in the tumor tissue was applied based on AngioSense. The tumor-bearing leg was immersed in the 43°C water for preheating, and TSLs were injected intravenously. Real-time monitoring of intratumoral (i.t.) DOX penetration could be performed, and it showed the progressing DOX wave front via its native fluorescence, labeling successively all cell nuclei. Cell uptake rates (1/k) of 3 minutes were found (n=241 cells), and a released-DOX penetration in the range of 2500 µm2·s−1 was found in the tumor extravascular space. This study also showed that not all vessels, identified as functional based on AngioSense, gave rise to local DOX penetration.
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