During the evaluation period, the novel H7N9 virus caused severe illness, including pneumonia and ARDS, with high rates of ICU admission and death. (Funded by the National Natural Science Foundation of China and others.).
Purpose
The purpose of this study was to characterize tissue-specific alterations in metabolism of hyperpolarized (HP) gluconeogenic precursors 13C-lactate and 13C-pyruvate by rat liver and kidneys under conditions of fasting or insulin-deprived diabetes.
Methods
Seven normal rats were studied by MR spectroscopic imaging of both HP 13C-lactate and 13C-pyruvate in both normal fed and 24 h fasting states, and seven additional rats were scanned after induction of diabetes by streptozotocin (STZ) with insulin withdrawal. Phosphoenolpyruvate carboxykinase (PEPCK) expression levels were also measured in liver and kidney tissues of the STZ-treated rats.
Results
Multiple sets of significant signal modulations were detected, with graded intensity in general between fasting and diabetic states. An approximate two-fold reduction in the ratio of 13C-bicarbonate to total 13C signal was observed in both organs in fasting. The ratio of HP lactate-to-alanine was markedly altered, ranging from a liver-specific 54% increase in fasting, to increases of 69% and 92% in liver and kidney, respectively, in diabetes. Diabetes resulted in a 40% increase in renal lactate signal. STZ resulted in 5.86-fold and 2.73-fold increases in PEPCK expression in liver and kidney, respectively.
Conclusion
MRI of HP 13C gluconeogenic precursors may advance diabetes research by clarifying organ-specific roles in abnormal diabetic metabolism.
13C steady state free precession (SSFP) magnetic resonance imaging and effective spin-spin relaxation time (T2) mapping were performed using hyperpolarized [13C] urea and [13C, 15N2] urea injected intravenously in rats. 15N labeling gave large T2 increases both in solution and in vivo due to the elimination of a strong scalar relaxation pathway. The T2 increase was pronounced in the kidney, with [13C, 15N2] urea giving T2 values of 6.3±1.3 s in the cortex and medulla, and 11±2 s in the renal pelvis. The measured T2 in the aorta was 1.3±0.3 s. [13C] urea showed shortened T2 values in the kidney of 0.23±0.03 s compared to 0.28±0.03 s measured in the aorta. The enhanced T2 of [13C, 15N2] urea was utilized to generate large signal enhancement by SSFP acquisitions with flip angles approaching the fully refocused regime. Projection images at 0.94 mm in-plane resolution were acquired with both urea isotopes, with [13C, 15N2] urea giving a greater than four-fold increase in signal-to-noise ratio [13C] over urea.
Purpose
Balanced steady state free precession (bSSFP) sequences can provide superior SNR efficiency for hyperpolarized 13C MRI by efficiently utilizing the non-recoverable magnetization, but managing their spectral response is challenging in the context of metabolic imaging. A new spectrally selective bSSFP sequence was developed for fast imaging of multiple hyperpolarized 13C metabolites with high spatiotemporal resolution.
Methods
This novel approach for bSSFP spectral selectivity incorporates optimized short duration spectrally selective RF pulses within a bSSFP pulse train and a carefully chosen TR to avoid banding artifacts.
Results
The sequence enabled sub-second 3D dynamic spectrally selective imaging of 13C metabolites of co-polarized [1-13C]pyruvate and [13C]urea at 2mm isotropic resolution, with excellent spectral selectivity (~100:1). The sequence was successfully tested in phantom studies and in vivo studies with normal mice.
Conclusion
This sequence is expected to benefit applications requiring dynamic volumetric imaging of metabolically active 13C compounds at high spatiotemporal resolution including preclinical studies at high field and potentially clinical studies.
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