Dual-mode IVUS transducer for image-guided brain therapy: preliminary experiments

Abstract

In this study, we investigated the feasibility of using 3.5-Fr intravascular ultrasound (IVUS) catheters for minimally-invasive, image-guided hyperthermia treatment of tumors in the brain. Feasibility was demonstrated by: (1) retro-fitting a commercial 3.5-Fr IVUS catheter with a 5 × 0.5 × 0.22 mm PZT-4 transducer for 9-MHz imaging and (2) testing an identical transducer for therapy potential with 3.3-MHz continuous-wave excitation. The imaging transducer was compared with a 9-Fr, 9-MHz ICE catheter when visualizing the post-mortem ovine brain and was also used to attempt vascular access to an in vivo porcine brain. A net average electrical power input of 700 mW was applied to the therapy transducer, producing a temperature rise of +13.5°C at a depth of 1.5 mm in live brain tumor tissue in the mouse model. These results suggest that it may be feasible to combine the imaging and therapeutic capabilities into a single device as a clinically-viable instrument.

Figure 1

Schematic of proposed dual-mode IVUS operation. Radial imaging field (gray circle) with tumor (white circle). Hyperthermia beam (straight lines indicate full beamwidth at half-maximum) from catheter (black circle) directed at tumor volume.

Figure 2

40-MHz image of 2.5-cm cyst phantom, acquired with Atlantis IVUS catheter. Arrows indicate cyst wall. Tick mark spacing is 1 mm.

Figure 3

Schematic of 9 MHz imaging prototype. (a) Top view of transducer bonded to metal housing (light gray). (b) Side view showing phenolic microballoon backing (dark gray). Scale in mm.

Figure 4

Catheter devices and 9-MHz images of 2.5-cm cyst phantom. (a) 9-Fr ICE with 2.1-mm-diameter transducer. (b) ICE catheter cyst image. (c) Modified IVUS prototype outside of 3.5-Fr sheath. (d) Modified IVUS cyst image. Tick mark spacing is 16 mm.

Figure 5

Diagram of ovine brain imaging scheme. Catheter insertion (McDannold et al.) into posterior portion of superior sagittal sinus, with rotating transducer scanning a perpendicular plane (dark blue). Reproduced with permission (Miselis 2006).

Figure 6

Therapy experiment procedures. (a) 40-MHz VisualSonics image verifying thermocouple needle 1 mm beneath the surface in tissue-mimicking material. (b) In vitro therapy experiment setup. (c) In vivo glioblastoma therapy setup: anesthetized mouse on foil-lined heating pad. Arrow indicates transducer position.

Figure 7

Post-mortem ovine brain 9-MHz imaging comparison showing lateral ventricles. (a) 9-Fr ICE catheter image. (b) Anatomical diagram, reproduced with permission (Fletcher et al. 2006). (c) 3.5-Fr modified IVUS prototype image. Tick mark spacing is 16 mm.

Figure 8

In vivo porcine imaging results. (a) Angiogram showing modified IVUS prototype (arrow) in right vertebral artery. (b) 9-MHz image of vertebral artery lumen (arrow) and surrounding tissue near subclavian junction. Tick mark spacing is 16 mm.

Figure 9

Thermocouple data from in vitro therapy experiment with tissue-mimicking material. Resulting temperature rise was 6.7°C in under 2 minutes.

Figure 10

Thermocouple data showing sequential temperature rises in excised glioblastoma tumor of 19.1°C, 9.2°C, and 4.9°C after 90 seconds of on-time for power levels of 700, 350, and 175 mW, respectively.

Figure 11

Thermocouple data for in vivo xenograft glioblastoma tumor grown in the flank of a nude mouse, showing sequential temperature rises of 13.5°C, 6.8°C, and 3.0°C after 60 seconds of on-time for power levels of 700, 350, and 175 mW, respectively.

Figure 12

In vivo porcine vascular imaging results. (a) Angiogram showing a regional hematoma (arrows) surrounding the right vertebral artery. (b) Volcano ChromoFlo image showing non-uniform flow (arrow) in the lumen near the vessel puncture site, acquired with 20-MHz Eagle Eye Gold. Tick mark spacing is 1 mm.

Figure 13

In vivo porcine brain imaging results. (a) Volcano PV018 image showing bordering skull (red arrow) and three gyri in close proximity (green arrows). Tick mark spacing is 2 mm. (b) Anatomical diagram, reproduced with permission (Welker 2011).