Development of an endoluminal high-intensity ultrasound applicator for image-guided thermal therapy of pancreatic tumors

Abstract

An ultrasound applicator for endoluminal thermal therapy of pancreatic tumors has been introduced and evaluated through acoustic/biothermal simulations and ex vivo experimental investigations. Endoluminal therapeutic ultrasound constitutes a minimally invinvasive conformal therapy and is compatible with ultrasound or MR-based image guidance. The applicator would be placed in the stomach or duodenal lumen, and sonication would be performed through the luminal wall into the tumor, with concurrent water cooling of the wall tissue to prevent its thermal injury. A finite-element (FEM) 3D acoustic and biothermal model was implemented for theoretical analysis of the approach. Parametric studies over transducer geometries and frequencies revealed that operating frequencies within 1-3 MHz maximize penetration depth and lesion volume while sparing damage to the luminal wall. Patient-specific FEM models of pancreatic head tumors were generated and used to assess the feasibility of performing endoluminal ultrasound thermal ablation and hyperthermia of pancreatic tumors. Results indicated over 80% of the volume of small tumors (~2 cm diameter) within 35 mm of the duodenum could be safely ablated in under 30 minutes or elevated to hyperthermic temperatures at steady-state. Approximately 60% of a large tumor (~5 cm diameter) model could be safely ablated by considering multiple positions of the applicator along the length of the duodenum to increase coverage. Prototype applicators containing two 3.2 MHz planar transducers were fabricated and evaluated in ex vivo porcine carcass heating experiments under MR temperature imaging (MRTI) guidance. The applicator was positioned in the stomach adjacent to the pancreas, and sonications were performed for 10 min at 5 W/cm² applied intensity. MRTI indicated over 40°C temperature rise in pancreatic tissue with heating penetration extending 3 cm from the luminal wall.

Keywords: MR guided ultrasound; catheter-based ultrasound; endoluminal; pancreatic cancer; thermal modeling; thermal therapy; ultrasound ablation.

Figure 1

Schema and concepts of an endoluminal ultrasound applicator positioned in the GI tract for thermal therapy of pancreatic tumors.

Figure 2

Cross-sectional slice of 3D generalized tissue block model for parametric studies of thermal ablation across transducer geometries and frequencies.

Figure 3

Effects of transducer configuration and operating frequency on (a) penetration depth (as measured from inner luminal wall) of thermal lesion, (b) tumor lesion volume (t₄₃ > 240 EM), and (c) maximum temperature of luminal wall tissue, after a single 5 minute sonication with a temperature set-point of 80°C.

Figure 4

(a) Patient-specific model anatomy #1, consisting of a small pancreatic head tumor directly adjacent to the duodenum. The applicator was positioned in the duodenal lumen, and ablation treatments were simulated using 2 MHz planar and lightly curvilinear transducer configurations. The ablated tissue margins, as defined by the t₄₃> 240 EM margins, are shown across the central cross-section for both cases (b). Hyperthermia was simulated using a 1 MHz tubular transducer, with temperature distributions and contours shown in (c).

Figure 5

(a) Patient-specific model anatomy #2, consisting of a small pancreatic head tumor adjacent to the SMA, stented bile duct, and pancreatic duct. (b) 240 EM dose contours for ablation, simulated by minutely translating and rotating a strongly focused curvilinear transducer to maximize tumor coverage while sparing all sensitive structures. (c) Tumor surface temperature distribution for a hyperthermia simulation, by rotating an applicator with a planar 1.5 MHz transducer.

Figure 6

Patient-specific model anatomy #3, consisting of a large pancreatic head tumor. For ablation, the applicator was translated to three distinct positions along the length of the duodenum and rotated at each position. (b) 240 EM dose contours obtained for an ablation simulation using a 2 MHz planar transducer. (c) Hyperthermia was simulated by rotating a single applicator with a 1.5 MHz planar transducer at position 1, with temperature distributions and contours shown across the central cross-section.

Figure 7

(a) Top view of distal tip of applicator, showing the transducer stage fixture with two mounted 10 mm × 10 mm 3.2 MHz planar transducers. (b) Side view of distal tip of applicator, showing the frontal coupling balloon above the mounted transducers and guiding tip.

Figure 8

(a) T2-weighted axial image of porcine carcass with the endoluminal ultrasound applicator positioned in the stomach lumen adjacent to the pancreas. Sonication was performed with real-time, multi-slice MRTI for a 10 min heating duration at 5 W/cm² applied intensity. Temperature elevation profiles are shown at the end of heating for a sagittal imaging plane (b) and two axial imaging planes (c)-(d) all with respect to the applicator.