High-Intensity Focused Ultrasound: Current Status for Image-Guided Therapy

Abstract

Image-guided high-intensity focused ultrasound (HIFU) is an innovative therapeutic technology, permitting extracorporeal or endocavitary delivery of targeted thermal ablation while minimizing injury to the surrounding structures. While ultrasound-guided HIFU was the original image-guided system, MR-guided HIFU has many inherent advantages, including superior depiction of anatomic detail and superb real-time thermometry during thermoablation sessions, and it has recently demonstrated promising results in the treatment of both benign and malignant tumors. HIFU has been employed in the management of prostate cancer, hepatocellular carcinoma, uterine leiomyomas, and breast tumors, and has been associated with success in limited studies for palliative pain management in pancreatic cancer and bone tumors. Nonthermal HIFU bioeffects, including immune system modulation and targeted drug/gene therapy, are currently being explored in the preclinical realm, with an emphasis on leveraging these therapeutic effects in the care of the oncology patient. Although still in its early stages, the wide spectrum of therapeutic capabilities of HIFU offers great potential in the field of image-guided oncologic therapy.

Keywords: HIFU; ablation; focused ultrasound surgery; image guided; interventional oncology; interventional radiology.

Fig. 1

Classical thermal lesion formed by focused US surgery (US absorption only) on porcine liver specimen. (a) Cigar-shaped thermal lesion is formed at focal zone of US wave pathway (two overlaid triangles) following HIFU single exposure. (b) Final thermal lesion after stacking each single lesion. Single lesions are much smaller than clinically common tumors and therefore each thermal lesion should be stacked compactly without leaving intervening viable tissue. This lesion can cover the entire pathological lesion as well as having a very sharp margin that could be controlled easily. (Reprinted with permission from Kim YS, Rhim H, Choi MJ, Lim HK, Choi D. High-intensity focused ultrasound therapy: an overview for radiologists. Korean J Radiol 2008; 9(4):291–302.)

Fig. 2

Ways a phased-array transducer can be used include producing multiple focal spots to increase the ablated volume per sonication, steering the focal point to different locations, and correcting for aberrations caused by tissue structures in the ultrasound beam path. (Reprinted with permission from Tempany et al.12)

Fig. 3

MR-guided HIFU volumetric ablation. (a) Schematic of HIFU transducer and beam, applying focused acoustic energy in concentric circles within a treatment cell. (b) Treatment cells 4, 8, or 12 mm in diameter, with a ratio of cell diameter to length of ∼1:2.5. (Reprinted with permission from Venkatesan et al.43)

Fig. 4

Intraprocedural MR-guided HIFU monitoring and MR imaging and histopathologic findings after leiomyoma ablation with MR-guided HIFU. (a–d) Graphic user interface displays multiplanar three-dimensional T2-weighted imaging and overlaid temperature maps (a–b) and overlaid thermal dose estimates (c–d) during sonication of an anterior intramural leiomyoma within the body of the uterus. Accumulated thermal dose information in the treated volume is displayed at the end of each sonication as a thermal dose estimate. These thermal doses are reported in CEM43, with 30 CEM43 (beige polygon, c–d) corresponding to onset of tissue alteration and 240 CEM43 (white polygon, c–d) representing predicted territory of complete necrosis. Both 30 CEM43 and 240 CEM43 thermal dose estimates are updated after each sonication. (e–f) Sagittal (e) and coronal (f) contrast-enhanced MR images after HIFU show nonenhancing treated region (black arrows). (g) Bivalved gross uterine specimen shows hemorrhagic necrosis in the area of treatment (white arrow). (h–j) Low-magnification (4 × ) histologic images of margin (h), high-magnification (10 × ) images of margin (j), and high-magnification images of the center of the ablation zone (j) confirm necrosis (asterisk) and narrow zone of transition (white arrows) between viable and necrotic HIFU-treated tissue. (Reprinted with permission from Venkatesan et al.43)

Fig. 5

A 68-year-old man with low-risk organ confined prostate cancer (prostate-specific antigen nadir, 8; Gleason score, 6–3 + 3) indicated to radical prostatectomy was included in a phase I trial for MR-guided HIFU treatment before surgery. (a) At treatment time, prostate cancer was visible at 3 T MR images that were used for treatment planning. The system automatically generates a lesion-specific sonication program that spares normal prostate parenchyma for focal ablation. More importantly, the system spares the rectal wall, preventing local parietal damage through active intrarectal cooling and real-time temperature mapping at treatment. (b) Immediately after treatment, gadolinium-enhanced T1-weighted image was acquired for treatment efficacy and safety control. The ablated volume appears as a nonperfusing area (yellow arrow) with intact adjacent rectal wall. Surgery after MR-guided FUS treatment was performed without treatment-related complications or operator difficulties. (Reprinted with permission from Napoli et al.50)

Fig. 6

Uterine fibroid in a 37-year-old woman who reported aggravated urinary frequency for 1 year treated with volumetric MR-guided HIFU ablation. (a) Baseline sagittal T2-weighted MR image shows large subserosal uterine fibroid (star) (11.6 cm, 446.7 mL) with signal intensity higher than that of skeletal muscle but lower than that of myometrium. (b) Sagittal MR thermometric image obtained during sonication with a 16-mm treatment cell (sonication frequency, 1.2 MHz; acoustic power, 140 W). Temperature maps and automatically drawn 240 EM thermal dose contours (white lines) that were formed by one sonication are shown. Thermal dose contours were shifted slightly anteriorly, presumably because of a near-field heating effect; however, contours were well within the fibroid margin. Low-temperature color pixels outside the heating area represent noise. A = center of treatment cell, yellow lines = 30 EM thermal dose contours. (c) Sagittal T2-weighted MR image at 3-month follow-up shows obvious volume shrinkage of fibroid tumor (star) (42.5% baseline). (Reprinted with permission from Kim et al.67)

Fig. 7

A 68-year-old woman with hypovascular HCC in the VI hepatic segment, previously resected for a single nodule at the left lobe, refused another surgery. It was proposed that she undergo MR-guided FUS treatment of an acoustically accessible lesion. Contrast-enhanced axial CT image shows a hypovascular hepatocellular carcinoma (white arrow) in the VI segment during arterial (a), portal venous (b), and late venous phase (c). The treatment was performed under general anesthesia, with the patient positioned the right lateral decubitus to reduce liver movement and to achieve wider contact between the abdominal wall and the transducer surface. Pretreatment localization of the tumor is demonstrated with contrast-enhanced acquisition (d), with posttreatment visualization of the nonperfused area (e). (Reprinted with permission from Napoli et al.50)

Fig. 8

Dynamic contrast-enhanced gradient-echo T1-weighted MR images (180/6.0, 90-degree flip angle, 128 × 256 matrix, 10-mm-thick sections, 2-mm intersection gap, one signal acquired, and 18-second acquisition time) obtained with breath holding from a 48-year-old man who underwent high-intensity focused ultrasound ablation for advanced pancreatic cancer. The tumor was 4.5 × 4.5 cm in diameter and located in the body of the pancreas. (a) Image obtained before high-intensity focused ultrasound shows the blood supply in the pancreatic lesion (arrowhead). (b) Image obtained 2 weeks after high-intensity focused ultrasound shows no evidence of contrast enhancement in the treated lesion (arrowhead), which is indicative of complete coagulation necrosis in the pancreatic cancer. (Reprinted with permission from Wu et al.97)

Fig. 9

MR images show complete response at long-term follow-up of a breast fibroadenoma (circled area) treated with MR imaging-guided FUS (a–d), T2-weighted fat-suppressed fast SE images (a–c: 2,500/100; d: 3,850/100) and (e–h), T1-weighted fat-suppressed postcontrast images (e, f: 600/12; g: 400/12; h: 517/12) obtained 2 months before therapy and at 7 days, 6 months, and 3 years after therapy, respectively. (Reprinted with permission from Hynynen et al.111)

Fig. 10

Basic concept of HIFU-induced tissue change by hyperthermia. As US waves are focused onto small spot, acoustic pressure is rapidly elevated near focus where tissue temperatures are also raised to level that is sufficient for thermotherapeutic effects, resulting in coagulation necrosis. (Reprinted with permission from Kim YS, Rhim H, Choi MJ, Lim HK, Choi D. High-intensity focused ultrasound therapy: an overview for radiologists. Korean J Radiol 2008;9(4):291–302.)

Fig. 11

Schematic drawing of US-induced gene therapy. When plasmid DNA-containing microbubbles are passed through blood vessels adjacent to diseased cells, insonated US waves rupture microbubbles and release plasmid DNA. Released DNA penetrates into cell through membranes by means of sonoporation. (Reprinted with permission from Kim YS, Rhim H, Choi MJ, Lim HK, Choi D. High-intensity focused ultrasound therapy: an overview for radiologists. Korean J Radiol 2008;9(4):291–302.)