<i>In vivo</i> 13C-MRI using SAMBADENA

<div><p>Magnetic Resonance Imaging (MRI) is a powerful imaging tool but suffers from a low sensitivity that severely limits its use for detecting metabolism <i>in vivo</i>. Hyperpolarization (HP) methods have demonstrated MRI signal enhancement by several orders of magnitude, enabling the detection of metabolism with a sensitivity that was hitherto inaccessible. While it holds great promise, HP is typically relatively slow (hours), expensive (million $, €) and requires a dedicated device (“polarizer”). Recently, we introduced a new method that creates HP tracers without an external polarizer but within the MR-system itself based on <i>para</i>hydrogen induced polarization (PHIP): Synthesis Amid the Magnet Bore Allows Dramatically Enhanced Nuclear Alignment (SAMBADENA). To date, this method is the simplest and least cost-intensive method for hyperpolarized ¹³C-MRI. HP of <i>P</i>_13C > 20% was demonstrated for 5mM tracer solutions previously. Here, we present a setup and procedure that enabled the first <i>in vivo</i> application of SAMBADENA: Within seconds, a hyperpolarized angiography tracer was produced and injected into an adult mouse. Subsequently, fast ¹³C-MRI was acquired which exhibited the vena cava, aorta and femoral arteries of the rodent. This first SAMBADENA <i>in vivo</i> ¹³C-angiography demonstrates the potential of the method as a fast, simple, low-cost alternative to produce HP-tracers to unlock the vast but hidden powers of MRI.</p></div

SAMBADENA HP of ¹³C HEP and subsequent ¹³C-MRI <i>in vivo</i>.

<p>¹³C-MRI (a), ¹H-MRI (b), ¹H-¹³C co-registration (c) and schematic view (d) of a living mouse after the injection of ~80 mM HEP in 150 μl H₂O (<i>P</i> ≈ 4% at the time of MRI). Strong ¹³C signal with an SNR of 35 was detected (a). A <i>T</i>₂-weighted ¹H-MRI (b) was acquired and co-registered with the ¹³C-image (c). The signal may be attributed to the <i>vena cava</i>, aorta and femoral arteries as shown schematically in (d). The isocenter of the magnet was the center of the images. Note that the tracer did not leave the magnet. [d): adapted with permission from <a href="http://www.biologycorner.com/" target="_blank">www.biologycorner.com</a> published under CC BY-NC-SA 4.0 license].</p

Picture and schematic view of the setup that allowed hyperpolarization and imaging within seconds.

<p>The SAMBADENA reactor was combined with a custom-built mouse bed and mounted to a motorized slider. The mouse bed allowed monitoring, heating and anesthesia of the animal (a). For an <i>in vivo</i> experiment, HP was performed at ~80°C and 15 bar with the reactor in the isocenter (Position 1, b). Subsequently, the pressure was released from the reactor, the temperature was adjusted to (35 ± 1)°C and the agent was ejected into a syringe. The setup was moved using the motorized slider until the animal was in the isocenter (Position 2, c). Simultaneously, manual injection was performed. Note that different shim settings that were obtained before were used for the two positions. About 15 s after HP, imaging was commenced.</p

Dynamic ¹³C-MRI acquired during the injection of a SAMBADENA-produced agent.

<p>Ten images were recorded using Setup 2 with a repetition time of <i>T</i>_R = 3 s and an acquisition time of each image of ~500ms during the injection of ~ 600 μl tracer solution into a test object (HP solution: 5 mM HEA, 2 mM catalyst in H₂O, <i>t</i>_h = 5 s; test object described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0200141#pone.0200141.s005" target="_blank">S4 Fig</a>). Injection was started after the first scan and ended after the sixth (15s). Note that the injection was paused for MRI. After each scan, the magnetization was flipped back towards the longitudinal direction to conserve magnetization. The signal of all images was normalized with respect to the highest signal of image No. 6; the colour scale was trimmed to 0–0.5 of the maximum intensity to visualize the signal in the small hose. ¹³C-MRI parameters: 90/180°, RARE-factor: 38, FOV: (8.4cm)², acquisition matrix of 96x96 px, interpolated to 256x256 px, in-plane resolution: 0.33 x 0.33 mm, one slice with a thickness of 6 cm, <i>T</i>_R = 0.487 s, <i>T</i>_E = 79 ms, acquisition time: 0.487 s.</p

sj-docx-1-ine-10.1177_15910199221145985 - Supplemental material for The effect of the size of the new contour neurovascular device for altering intraaneurysmal flow

Supplemental material, sj-docx-1-ine-10.1177_15910199221145985 for The effect of the size of the new contour neurovascular device for altering intraaneurysmal flow by Mariya S Pravdivtseva, Andrey N Pravdivtsev, Sönke Peters, Johannes Hensler, Naomi Larsen, Jan-Bernd Hövener, Olav Jansen and Fritz Wodarg in Interventional Neuroradiology</p

3D maximum-intensity-projection ZTE MRI and approximate coil positions (left) acquired at 9.4 T and photograph of coil assembled from CB₂ and LG₂ (right), either with a conventional BNC connector and coaxial cable (top), or a custom-made PTFE cable that was soldered to the circuit board (bottom).

<p>Note that the signal originating from the BNC connector was removed using the custom build cable. In turn, signal originating from the variable capacitors appeared close to the noise level (FOV = 20 cm).</p

Dimensions of exchangeable loop-gap (LG) inductors that were mounted on the circuit boards (CB) and sensitive volume of the commercial quadrature birdcage resonators (QR₁ and QR₂) and linearly-polarized birdcage resonator (LR).

<p>Dimensions of exchangeable loop-gap (LG) inductors that were mounted on the circuit boards (CB) and sensitive volume of the commercial quadrature birdcage resonators (QR₁ and QR₂) and linearly-polarized birdcage resonator (LR).</p

Photographs and schematics of the single-tune circuit boards (CB₁, left and CB₂, center) and dual-tune circuit board (CB₃, right) with and without loop-gap (LG) inductors.

<p>Conventional BNC connectors (left and right) as well as a custom-made PTFE coaxial cable with low hydrogen content are shown (center). Values of variable capacitors are: C_V1,3-9 = 0.3–3.5 pF, C_V2,10,11 = 1.1–16 pF; fixed-value capacitors: C_F1 = 1 pF, C_F2 = 100 pF, C_F3 = 6.8 pF, C_F1 = 10 pF; inductors: L_1,2 = 22 nH.</p

Representative photograph of several loop-gap inductors that were constructed (LG_1–6). Note the ledges used for connection. Dimensions are provided in Table 2.

<p>Representative photograph of several loop-gap inductors that were constructed (LG_1–6). Note the ledges used for connection. Dimensions are provided in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0139763#pone.0139763.t002" target="_blank">Table 2</a>.</p

Signal, noise, signal-to-noise-ratio (SNR) and reference pulse power (<i>P</i>_W⁹⁰) of a 1 ms, 90°-pulse for the coils composed of a circuit board (CB) and loop-gap (LG) inductor, as well as for commercial coils that were polarized in quadrature (QR₁, QR₂) and linear (LR).

<p>Signal, noise, signal-to-noise-ratio (SNR) and reference pulse power (<i>P</i>_W⁹⁰) of a 1 ms, 90°-pulse for the coils composed of a circuit board (CB) and loop-gap (LG) inductor, as well as for commercial coils that were polarized in quadrature (QR₁, QR₂) and linear (LR).</p