Placental physiology monitored by hyperpolarized dynamic ¹³ C magnetic resonance

Abstract

Placental functions, including transport and metabolism, play essential roles in pregnancy. This study assesses such processes in vivo from a hyperpolarized MRI perspective. Hyperpolarized urea, bicarbonate, and pyruvate were administered to near-term pregnant rats, and all metabolites displayed distinctive behaviors. Little evidence of placental barrier crossing was observed for bicarbonate, at least within the timescales allowed by C relaxation. By contrast, urea was observed to cross the placental barrier, with signatures visible from certain fetal organs including the liver. This was further evidenced by the slower decay times observed for urea in placentas vis-à-vis other maternal compartments and validated by mass spectrometric analyses. A clear placental localization, as well as concurrent generation of hyperpolarized lactate, could also be detected for [1-C]pyruvate. These metabolites also exhibited longer lifetimes in the placentas than in maternal arteries, consistent with a metabolic activity occurring past the trophoblastic interface. When extended to a model involving the administration of a preeclampsia-causing chemical, hyperpolarized MR revealed changes in urea's transport, as well as decreases in placental glycolysis vs. the naïve animals. These distinct behaviors highlight the potential of hyperpolarized MR for the early, minimally invasive detection of aberrant placental metabolism.

Enhanced hyperpolarized chemical shift imaging based on a priori segmented information

“…Further quantitative aspects of these tests, including image correlations vs the reference image, the image contrast arising for both methods, and quantitative reliability issues, are summarized in Figure S1 and Tables S1 and S2 of the Supporting Information section. Figure 3 extends these measurements to 13 C MRSI tests, based on a 13 C 1 -enriched glucose sample. These reconstructions arise from the same data and focus on two spectral regions: one containing the glucose peaks and one containing noise.…”

“…Following the pyruvate's hyperpolarization, 800 µL of 80-mM 13 C 1 -pyruvate were injected in equal aliquots into the right-and left-hand side Eppendorf tubes, and a time series of 15 spectral images was collected over approximately 1.5 min. 13 C hyperpolarized MRSI experiments were also carried out in vivo, focusing on placentas of Wistar pregnant rats. Nine rats were scanned at days 17 to 21 of gestation, with pregnancy timed on the morning following overnight pairing of male/ female pairs.…”

“…These experiments were approved by the Institutional Animal Care and Use Committee of the Weizmann Institute of Science (IACUC Applications #34080217 and #36350617), and some of these data have been presented and the biological content analyzed in Ref. 13.…”

“…[42][43][44][45] Similarly, the PRO-SLAM algorithm hereby proposed uses iterations to complete the missing k-space data carrying the high-resolution features, while enforcing intracompartment smoothness in the image domain by minimizing amplitude gradients within each compartment. More specifically, let's assume that to accommodate a given (high) definition that is desired in 13 C MRSI one would have to collect data over -k max ≤ k ≤ + k max , but that for practical reasons data were only sampled for a central portion of k-space -k PRO_SLAM ≤ k ≤ + k PRO_SLAM , with k PRO_SLAM ≤ k max . The missing highfrequency samples in the |k PRO_SLAM | ≤ |k| ≤ |k max | interval define a convex set, in the sense that any linear combination of two images that respects the recorded central k-space data and fulfills intracompartment smoothness, will also be an image that belongs to this set.…”

“…3,4 This opens promising oncological perspectives, where hyperpolarized 13 C 1 -pyruvate and other substrates such as fructose and glucose are used to quantify the Warburg effect, thus localizing malignant tissue and evaluating treatment response. [2][3][4][5][6][7][8][9] Additional in vivo applications of hyperpolarized MRSI have included cardiac imaging, 10,11 examination of muscle function, 12 placental metabolism investigations 13 and the monitoring of perfusion -for instance by following the fate of 13 C-urea in kidneys, tumors and other organs. 14 The low toxicity of these metabolites, their stable isotope character and the lack of ionizing radiation, endow this MR approach with the prospect to evolve into a new form of metabolic molecular imaging, without some of the disadvantages associated to PET or CT.…”