Development of Magnetic Probe for Sentinel Lymph Node Detection in Laparoscopic Navigation for Gastric Cancer Patients

Abstract

New laparoscopic sentinel lymph node navigation using a dedicated magnetic probe and magnetic nanoparticle tracer for gastric cancer patients allows minimally invasive surgeries. By identifying the sentinel lymph nodes containing magnetic nanoparticles, patients can avoid excessive lymph node extraction without nuclear facilities and radiation exposure. This paper describes the development of the laparoscopic magnetic probe, ACDC-probe, for laparoscopic sentinel lymph node identification utilizing the nonlinear response of the magnetic nanoparticles magnetized by an alternating magnetic field with a static magnetic field. For highly sensitive detection, the ratio of static to alternating magnetic fields was optimized to approximately 5. The longitudinal detection length was approximately 10 mm for 140 μg of iron, and the detectable amount of iron was approximately 280 ng at a distance of 1 mm. To demonstrate the feasibility of laparoscopic detection using the ACDC-probe and magnetic tracers, an experiment was performed on a wild swine. The gastric sentinel lymph node was clearly identified during laparoscopic navigation. These results suggest that the newly developed ACDC-probe is useful for laparoscopic sentinel lymph node detection and this magnetic technique appears to be a promising method for future sentinel lymph node navigation of gastric cancer patients.

Figure 1

Magnetic technique for sentinel lymph node navigation in gastric cancer patients. (a) Medical instruments, such as forceps, camera, and a magnetic probe, are inserted using trocars. (b) Schematic of intraabdominal and laparoscopic identification of sentinel lymph nodes using a magnetic probe and magnetic tracers for gastric cancer patients. Sentinel lymph nodes containing magnetic tracers are detected by a magnetic probe laparoscopically.

Figure 2

(a) Magnetization M of MNPs (red solid line) and typical paramagnetic materials (black dashed line) as a function of an applied external magnetic field H. (b) Nonlinearity of the M-H curve derived by second derivatives of M-H curve: MNPs (red solid line) and paramagnetism (black dashed line).

Figure 3

(a) ACDC-probe prototype for laparoscopic detection of sentinel lymph node containing magnetic nanoparticles. Length of probe shaft is 400 mm and electric cables are connected to driving and detection circuits (see Fig. 4). (b) Diameter of the probe head is 12 mm to be inserted through the trocar for laparoscopic operation. (c) Schematic of the probe head; a drive coil and permanent magnet generates AC and DC magnetic fields, respectively, for magnetization of magnetic nanoparticles. Newly generated magnetic fields of MNPs are measured by a detection coil (two pick-up coils and a balancing coil). Longitudinal direction of the probe is Z-axis and lateral direction is R-axis.

Figure 4

Schematic of driving and detection systems. A permanent magnet generates DC magnetic fields. Drive coil generates AC magnetic fields (f₀ ~2.94 kHz) through a capacitance (~125 nF) for series resonance of f₀; sine waves of 37.5 mA are produced by a function generator. Second harmonics signals (f₂ ~5.88 kHz) detected through pick-up coils and a balancing coil is measured by lock-in amplifier via parallel resonance with a capacitance (~68 nF), a preamplifier (40 dB), and band pass filter (5.5–6.3 kHz). The digital voltmeter used for animal experiments detected the magnetic signal intensity and produced sounds based on the detected value (higher frequency sound for larger signal intensity).

Figure 5

Normalized output signals versus the ratio of DC and AC magnetic fields B_DC/B_AC with respect to the MNPs containing 140 μg of iron. Larger output signals were observed at B_DC/B_AC = 4–6 as shown a green shaded area. The maximum value was observed at the ratio B_DC/B_AC ~5. MNPs location is 3 mm from the probe head.

Figure 6

(a) Measured AC (blue solid line) and DC (black dashed line) magnetic fields as a function of distance from the probe head on Z-axis. (b) Ratio of B_DC/B_AC as a function of the distance from the probe head on Z-axis. At Z = 0–20 mm, the ratio is approximately 5–6.

Figure 7

(a) Two-dimensional, (b) longitudinal (R = 0 mm), and (c) lateral (Z = 0 mm) detection length with respect to MNPs of 5 μL (140 μg iron). Enlarged view on (b,c) represents a longitudinal and lateral detection length of approximately 10 and 11 mm, respectively. Error bar represents an average of three measurements. Noise level is approximately 1 nT.

Figure 8

Detection limit of the amount of iron located 1 mm apart from the probe head is approximately 280 ng. Error bar represents an average of three measurements (standard deviation is approximately 1 nT).

Figure 9

Detection performance of ACDC-probe (solid line) compared with DC-probe (dashed line) as a function of distance from the probe head on Z-axis. Detected signals from the MNPs (140 μg of iron) are normalized by the noise level of each probe (~1 nT for the ACDC-probe and ~1 μT for the DC-probe). Detailed of the DC-probe are described in ref. . Error bar represents an average of three measurements.

Figure 10

Comparison between (a) ACDC-probe and (b) DC-probe with respect to the detection of MNPs (red solid line: 140 μg of iron) and SUS304 (blue dashed line: a typical stainless-steel metal for medical instruments). Error bar represents an average of three measurements.

Figure 11

Animal experiment of laparoscopic detection involving developed ACDC-probe prototype in a swine (a wild-type swine, weight: 26.4 kg). Surgeon is finding LNs containing the MNPs by means of the laparoscopic instruments via trocars under the monitoring of laparoscopic camera in accordance with the displayed value and sound on voltmeter.

Figure 12

(a) Laparoscopic detection of SLN (#8a) using ACDC-probe prototype in the laparoscopic surgery. SLN (#8a) was detected by the probe, and the stomach was lifted up by forceps to find the SLNs. (b) Schematic of SLNs location in a stomach. (c) Excised lymph node with brownish-color of MNPs. (d) Magnetic strength of SLNs in laparoscopic detection (during operation) and ex-vivo (after extraction) detection.