High-Resolution Low-Field Molecular Magnetic Resonance Imaging of Hyperpolarized Liquids

Abstract

We demonstrate the feasibility of microscale molecular imaging using hyperpolarized proton and carbon-13 MRI contrast media and low-field (47.5 mT) preclinical scale (38 mm i.d.) 2D magnetic resonance imaging (MRI). Hyperpolarized proton images with 94 × 94 μm2 spatial resolution and hyperpolarized carbon-13 images with 250 × 250 μm2 in-plane spatial resolution were recorded in 4–8 s (largely limited by the electronics response), surpassing the in-plane spatial resolution (i.e., pixel size) achievable with micro-positron emission tomography (PET). These hyperpolarized proton and 13C images were recorded using large imaging matrices of up to 256 × 256 pixels and relatively large fields of view of up to 6.4 × 6.4 cm2. 13C images were recorded using hyperpolarized 1-13C-succinate-d2 (30 mM in water, %P13C = 25.8 ± 5.1% (when produced) and %P13C = 14.2 ± 0.7% (when imaged), T1 = 74 ± 3 s), and proton images were recorded using 1H hyperpolarized pyridine (100 mM in methanol-d4, %PH = 0.1 ± 0.02% (when imaged), T1 = 11 ± 0.1 s). Both contrast agents were hyperpolarized using parahydrogen (>90% para-fraction) in an automated 5.75 mT parahydrogen induced polarization (PHIP) hyperpolarizer. A magnetized path was demonstrated for successful transportation of a 13C hyperpolarized contrast agent (1-13C-succinate-d2, sensitive to fast depolarization when at the Earth’s magnetic field) from the PHIP polarizer to the 47.5 mT low-field MRI. While future polarizing and low-field MRI hardware and imaging sequence developments can further improve the low-field detection sensitivity, the current results demonstrate that microscale molecular imaging in vivo is already feasible at low (<50 mT) fields and potentially at low (∼1 mM) metabolite concentrations.

In Situ and Ex Situ Low‐Field NMR Spectroscopy and MRI Endowed by SABRE Hyperpolarization

“…Indeed, P H = (1.6 ± 0.16) % was observed in a 5 mm medium-walled NMR tube filled with about 0.75 mL of solution compared to P H = (0.2 ± 0.02) % that was observed in a 10 mm NMR tube filled with about 3 mL of solution; this is in qualitative agreement with the in situ imaging studies. Notably, whereas our previous study (focusing primarily on enabling instrumentation technologies and imaging aspects of 1 H and 13 C hyperpolarized contrast media) [18] reported ex situ MRI images, this work additionally reports on the feasibility of in situ imaging of a real-time chemical reaction. Unlike our recent work [18] and the work of Hövener et al, [19] the in situ MRI shown herein (Figure 3 d) takes snapshots in real time instead of delays of around 8 s [18] or 4 s. [19] This is a clear advantage, because some species (e.g.…”

“…Notably, whereas our previous study (focusing primarily on enabling instrumentation technologies and imaging aspects of 1 H and 13 C hyperpolarized contrast media) [18] reported ex situ MRI images, this work additionally reports on the feasibility of in situ imaging of a real-time chemical reaction. Unlike our recent work [18] and the work of Hövener et al, [19] the in situ MRI shown herein (Figure 3 d) takes snapshots in real time instead of delays of around 8 s [18] or 4 s. [19] This is a clear advantage, because some species (e.g. HP orthohydrogen and HP Ir–dihydride) are short lived and because of the convenience of data acquisition.…”

“…A 1.6 mm OD capillary was used for p -H 2 bubbling through this solution. The following imaging parameters were used for in situ 2D MRI (Figure 3 d) by using the gradient echo sequence supplied by the equipment manufacturer (Magritek, Wellington, New Zealand) during p -H 2 bubbling: acquisition time = 6.4 ms, echo time (TE) = 7 ms, repetition time (TR) = 200 ms, field of view (FOV) = 96 × 96 mm 2 , spectral width (SW) = 20 kHz, imaging matrix = 128 × 128, RF pulse of 15 µs (α = 15°), number of averages (NA) = 32, 33 % of k -space sampling (under-sampling did not induce any visible imaging artifacts but reduced the total imaging time significantly), [18] which resulted in effective spatial and temporal resolutions of 0.75 × 0.75 mm 2 and 4.5 min, respectively. The following imaging parameters were used for ex situ 2D MRI (Figure 3 e, top) by using the gradient echo sequence after sample transfer into the 47.5 mT MRI system: acquisition time = 12.8 ms, TE = 13 ms, TR = 60 ms, FOV = 32 × 32 mm 2 , SW = 20 kHz, imaging matrix = 256 × 256, RF pulse of 10 µs (α = 9°), NA = 1, 50% of k -space sampling resulting in effective spatial and temporal resolutions of 0.125 × 0.125 mm 2 and 7.7 s. The imaging parameters for the image shown in Figure 3 e (bottom) were: acquisition time = 25.6 ms, TE = 26 ms, TR = 60 ms, FOV = 64 × 64 mm 2 , SW = 20 kHz, imaging matrix = 512 × 512, RF pulse of 10 µs (α = 9°), NA = 1, 20% of k -space sampling resulting in effective spatial and temporal resolutions of 0.125 × 0.125 mm 2 and about 6 s, respectively.…”

“…Building on our demonstration of in situ PHIP [17] spectroscopic detection and ex situ SABRE [18] MRI detection and the recent work of others, [14b, 19] herein we present high-resolution MRI imaging and spectroscopy of a SABRE chemical-exchange reaction by using a combination of in situ and ex situ low-field NMR/MRI approaches. Ex situ NMR spectra and MRI images of a liquid solution after exchange with p -H 2 were obtained at 47.5 mT with sub-millimeter in-plane spatial resolution (pixel size 125 × 125 µm 2 ) and a large imaging matrix of up to 512 × 512.…”

Adaptive suppression of power line interference in ultra-low field magnetic resonance imaging in an unshielded environment

“…The first SQUID-based ultra-low field (ULF) MRI system was built by the Clarke group at Berkeley, and operated at 132 μT [4]. Hyperpolarization techniques, which significantly enhance spin population difference, were introduced in LF/ULF nuclear magnetic resonance (NMR) and MRI systems to obtain stronger SNR [5][6][7]. Some potential applications of ULF MRI have been demonstrated compared with high field MRI, e.g., enhanced contrast between cancerous and surrounding tissues [8,9], the possibility of imaging in the presence of metallic objects [10], the hybrid biomagnetic imaging of MRI and magnetoencephalography (MEG) [11,12] and the feasibility of neuronal current imaging [13][14][15].…”