MR guided thermal therapy of pancreatic tumors with endoluminal, intraluminal and interstitial catheter-based ultrasound devices: Preliminary theoretical and experimental investigations

Abstract

Image-guided thermal interventions have been proposed for potential palliative and curative treatments of pancreatic tumors. Catheter-based ultrasound devices offer the potential for temporal and 3D spatial control of the energy deposition profile. The objective of this study was to apply theoretical and experimental techniques to investigate the feasibility of endogastric, intraluminal and transgastric catheter-based ultrasound for MR guided thermal therapy of pancreatic tumors. The transgastric approach involves insertion of a catheter-based ultrasound applicator (array of 1.5 mm OD x 10 mm transducers, 360° or sectored 180°, ~7 MHz frequency, 13-14G cooling catheter) directly into the pancreas, either endoscopically or via image-guided percutaneous placement. An intraluminal applicator, of a more flexible but similar construct, was considered for endoscopic insertion directly into the pancreatic or biliary duct. An endoluminal approach was devised based on an ultrasound transducer assembly (tubular, planar, curvilinear) enclosed in a cooling balloon which is endoscopically positioned within the stomach or duodenum, adjacent to pancreatic targets from within the GI tract. A 3D acoustic bio-thermal model was implemented to calculate acoustic energy distributions and used a FEM solver to determine the transient temperature and thermal dose profiles in tissue during heating. These models were used to determine transducer parameters and delivery strategies and to study the feasibility of ablating 1-3 cm diameter tumors located 2-10 mm deep in the pancreas, while thermally sparing the stomach wall. Heterogeneous acoustic and thermal properties were incorporated, including approximations for tumor desmoplasia and dynamic changes during heating. A series of anatomic models based on imaging scans of representative patients were used to investigate the three approaches. Proof of concept (POC) endogastric and transgastric applicators were fabricated and experimentally evaluated in tissue mimicking phantoms, ex vivo tissue and in vivo canine model under multi-slice MR thermometry. RF micro-coils were evaluated to enable active catheter-tracking and prescription of thermometry slice positions. Interstitial and intraluminal ultrasound applicators could be used to ablate (t₄₃>240 min) tumors measuring 2.3-3.4 cm in diameter when powered with 20-30 W/cm² at 7 MHz for 5-10 min. Endoluminal applicators with planar and curvilinear transducers operating at 3-4 MHz could be used to treat tumors up to 20-25 mm deep from the stomach wall within 5 min. POC devices were fabricated and successfully integrated into the MRI environment with catheter tracking, real-time thermometry and closed-loop feedback control.

Keywords: MR temperature imaging; ablation; hyperthermia; modeling; pancreatic cancer; ultrasound.

Figure 1

The general schema and concepts for catheter-based ultrasound devices for MR guided ablation or hyperthermia of pancreas tumors. (a) Interstitial transgastric applicator as inserted via an endoscope into a pancreatic tumor, similar to endoscopic biopsy. Similarly, an intraluminal applicator can be inserted directly into the pancreatic duct. (b) Larger endoluminal device positioned with the stomach or duodenum with acoustic energy directed toward tumor target.

Figure 2

Simulated ablation zones from a 3x360° and 3x180° directional interstitial ultrasound applicator inserted within desmoplastic pancreatic tumor volumes surrounded by normal pancreas tissue, after 5 min. Applied power to elements can be independently controlled to tailor the length and radial penetration. The directional applicators can be applied to protect regions of tissue (such as a duct).

Figure 3

Parametric simulations of temperature distributions and thermal dose contours (t₄₃>240 min) for (a) cylindrical, (b) planar and (c) curvilinear transducer configurations under consideration, operated at 3 MHz with 10–22°C cooling.

Figure 4

Patient-specific models depicting interstitial ultrasound ablation of pancreatic tumors in the tail and head of the pancreas. A transgastric approach is applied for the (top row) tail, and a trans-duodenal approach is used for the head (bottom row). Multi-element multi-sector devices were applied to coagulate 2 cm diameter tumor volumes in under 5 min. 3D anatomy and final temperature distributions are depicted.

Figure 5

Patient-specific model of endgastric ultrasound ablation of a pancreatic tumor in the head of the pancreas. (a) and (b) show the anatomy and tumor location in a CT scan and 3D model, respectively. (c) depicts simulations of temperature distributions and thermal dose contours (t₄₃>240 min) transducers operated at 3 MHz with 10°C cooling.

Figure 6

Patient specific simulations of intraductal ultrasound depicting (a) anatomy and location of tumor and applicator within the pancreatic duct, (b) ablative temperature isosurface under 5 min of ablation and (c) steady-state hyperthermia temperatures (>40°C) extending beyond tumor boundary.

Figure 7

Initial proof-of-concept devices: (a) interstitial device for transgastric insertion and (b) endoluminal device for placement within stomach or duodenum adjacent to pancreas.

Figure 8

Multi-slice MRTI for monitoring and control of transgastric interstitial heating shown (top) within tissue equivalent phantom and (bottom) within in vivo canine muscle, demonstrating penetrating and effective directional heating patterns with control along the length and angle of the applicator.

Figure 9

Multi-slice MRTI for monitoring and control of an endoluminal applicator with a planar transducer shown (top) within tissue equivalent phantom and (bottom) within ex vivo porcine muscle (a pancreas tumor mimic) surrounded by porcine stomach, demonstrating MR compatibility as well as penetrating and effective directional heating patterns through the stoma ach and into the surrounding tissue.

Figure 10

Two types of coils, (left) angled oblique and pancake coils, were evaluated for active MR tracking of applicator position within ex vivo tissue. The applicator image (center) with the (right) high-signal spatial localization from the tracking coil could potentially be used to demarcate the precise position and orientation of the applicator within complex anatomy when setting up MRTI.