MRI guided and monitored focused ultrasound thermal ablation methods: a review of progress

Hynynen, Kullervo; McDannold, Nathan

doi:10.1080/02656730410001716597

Cited by 92 publications

(59 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One example is the split beam -focused transducer, which has been shown to heat volumes of tissue 3-to 4-fold greater than a single focused beam within the same time period (28). Another is the use of focused phased-array transducers (29), whose focus can be positioned and redirected much faster than traditional mechanical means, potentially treating multiple, adjacent regions of tissue during the relatively long ''OFF'' part of the pulse cycle.…”

Section: Discussionmentioning

confidence: 99%

Pulsed-High Intensity Focused Ultrasound and Low Temperature–Sensitive Liposomes for Enhanced Targeted Drug Delivery and Antitumor Effect

Dromi¹,

Frenkel²,

Luk³

et al. 2007

Clinical Cancer Research

440

314

View full text Add to dashboard Cite

Purpose:To determine if pulsed-high intensity focused ultrasound (HIFU) could effectively serve as a source of hyperthermia with thermosensitive liposomes to enhance delivery and efficacy of doxorubicin in tumors. Experimental Design: Comparisons in vitro and in vivo were carried out between nont hermosensitive liposomes (NTSL) and low temperature^sensitive liposomes (LTSL). Liposomes were incubated in vitro over a range of temperatures and durations, and the amount of doxorubicin released was measured. For in vivo experiments, liposomes and free doxorubicin were injected i.v. in mice followed by pulsed-HIFU exposures in s.c. murine adenocarcinoma tumors at 0 and 24 h after administration. Combinations of the exposures and drug formulations were evaluated for doxorubicin concentration and growth inhibition in the tumors. Results: In vitro incubations simulating the pulsed-HIFU thermal dose (42jC for 2 min) triggered release of 50% of doxorubicin from the LTSLs; however, no detectable release from the NTSLs was observed. Similarly, in vivo experiments showed that pulsed-HIFU exposures combined with the LTSLs resulted in more rapid delivery of doxorubicin as well as significantly higher i.t. concentration when compared with LTSLs alone or NTSLs, with or without exposures. Combining the exposures with the LTSLs also significantly reduced tumor growth compared with all other groups. Conclusions: Combining low-temperature heat-sensitive liposomes with noninvasive and nondestructive pulsed-HIFU exposures enhanced the delivery of doxorubicin and, consequently, its antitumor effects. This combination therapy could potentially produce viable clinical strategies for improved targeting and delivery of drugs for treatment of cancer and other diseases.The dose of drug required to achieve clinically effective cytotoxicity in tumors often causes severe damage to actively propagating nonmalignant cells, resulting in a variety of undesirable side effects (1). Abnormal and heterogeneous distribution of inefficient vasculature (2), high interstitial fluid pressures (3), and fibrillar collagen in the extracellular matrix (4) are some of the barriers that further complicate effective and uniform drug delivery to tumors. Novel paradigms to overcome these barriers with new drug and device combinations may present fertile ground for continued research.Employing drug delivery strategies, such as liposomal encapsulation, can optimize and enhance the delivery of different agents with lower systemic toxicity and better drug cell internalization compared with free drug (5). A smaller volume of distribution and prolonged clearance time may also be achieved by incorporating lipid-conjugated polyethylene glycol into the liposomal membrane. This polyethylene glycolylation provides a protective barrier against interactions with plasma proteins and the reticuloendothelial system, allowing for enhanced accumulation of the chemotherapeutic agent into tumors (6). Polyethylene glycolylated liposomes containing doxorubicin, or Doxil, have bee...

show abstract

Section: Discussionmentioning

confidence: 99%

Pulsed-High Intensity Focused Ultrasound and Low Temperature–Sensitive Liposomes for Enhanced Targeted Drug Delivery and Antitumor Effect

Dromi¹,

Frenkel²,

Luk³

et al. 2007

Clinical Cancer Research

440

314

View full text Add to dashboard Cite

show abstract

“…We and others are developing cross-modality imaging methods in which nuclear medicine, magnetic resonance imaging, and optical imaging probes are used to visualize the delivery vehicle or the model drug [51][52][53][54].The great strength of nuclear imaging techniques, particularly positron emission tomography, is the real-time and highly sensitive full-body pharmacokinetics currently possible in pre-clinical studies [54,55]. Magnetic resonance imaging (MRI) techniques can be used to visualize the biodistribution of drugs or vehicles [52] and the activation of delivery vehicles in limited cases [51], and MRI can also be used to monitor local temperature in pre-clinical and clinical studies [56]. Optical imaging can be broadly applied to monitor the activation of a delivery vehicle or release of a drug, although in vivo studies of ultrasound-based drug delivery do not yet incorporate real-time optical imaging.…”

Section: Other Issuesmentioning

confidence: 99%

Driving delivery vehicles with ultrasound

Ferrara

2008

Advanced Drug Delivery Reviews

228

162

View full text Add to dashboard Cite

Therapeutic applications of ultrasound have been considered for over 40 years, with the mild hyperthermia and associated increases in perfusion produced by ultrasound harnessed in many of the earliest treatments. More recently, new mechanisms for ultrasound-based or ultrasound-enhanced therapies have been described, and there is now great momentum and enthusiasm for the clinical translation of these techniques. This dedicated issue of Advanced Drug Delivery Reviews, entitled "Ultrasound for Drug and Gene Delivery," addresses the mechanisms by which ultrasound can enhance local drug and gene delivery and the applications that have been demonstrated at this time. In this commentary, the identified mechanisms, delivery vehicles, applications and current bottlenecks for translation of these techniques are summarized. KeywordsUltrasound; Therapy; Drug delivery; Gene delivery; Sonoporation; Cavitation As an imaging modality, ultrasound is widely employed and valued for its real time applications, low cost, simplicity, and safety. Waves of alternating increased and decreased pressure propagate from the transducer, typically resulting in a maximum intensity in a focal region chosen by the operator. The dimensions of the focal region can vary from tens of microns for high frequency ultrasound to centimeters for an unfocused therapeutic beam. Most clinical instruments are engineered to effectively image from the body surface to 24 or more centimeters in depth. The ability to locally control and maximize energy deposition deep within the body facilitates a broad range of clinical opportunities for ultrasound imaging and therapy. Developing over four decades, clinical and commercial application of ultrasonic therapies spans hyperthermia, drug delivery, lipoplasty, and thrombolysis [1,2]. A complete and precise summary of the potential applications for ultrasonic enhancement of drug and gene delivery remains challenging as the mechanisms are multiple and not fully characterized. From an engineering viewpoint, the methods by which ultrasound facilitates drug and gene delivery can be summarized as direct changes in the biological or physiological properties of tissues facilitating transport, direct changes in the drug or vehicle increasing bioavailability or enhancing efficacy, and indirect effects by which ultrasound acts on the vehicle to produce changes in the surrounding tissue. While there are common mechanisms between these methods, the engineering challenges associated with the optimization of ultrasound systems and drug and vehicle design are unique for each method. Promising examples of each of these methods can be identified at this time and are addressed below.☆ This commentary is part of the Advanced Drug Delivery Reviews theme issue on "Ultrasound in Drug and Gene Delivery".

show abstract

“…In conventional devices of focused ultrasound therapy, magnetic resonance imaging (MRI) and ultrasonic imaging have been used for treatment monitoring. 12,13) Since the lifetime of cavitation bubbles is on the order of 1 ms and up to the order of 10 ms even under sustained oscillation for maintaining the presence of bubbles, [14][15][16] the guidance by high-speed ultrasonic imaging achieving a frame rate of more than 1 kfps using unfocused transmission is promising. [17][18][19][20] Microbubbles such as cavitation bubbles are known to oscillate nonlinearly, and harmonic imaging is widely used for their detection.…”

Section: Introductionmentioning

confidence: 99%

Selective detection of cavitation bubbles by triplet pulse sequence in high-intensity focused ultrasound treatment

Iwasaki

Nagaoka

Yoshizawa

et al. 2018

Jpn. J. Appl. Phys.

View full text Add to dashboard Cite

Acoustic cavitation bubbles are known to enhance the heating effect in high-intensity focused ultrasound (HIFU) treatment. The detection of cavitation bubbles with high sensitivity and selectivity is required to predict the therapeutic and side effects of cavitation, and ensure the efficacy and safety of the treatment. A pulse inversion (PI) technique has been widely used for imaging microbubbles through enhancing the second-harmonic component of echo signals. However, it has difficulty in separating the nonlinear response of microbubbles from that due to nonlinear propagation. In this study, a triplet pulse (3P) method was investigated to specifically image cavitation bubbles by extracting the 1.5th fractional harmonic component. The proposed 3P method depicted cavitation bubbles with a contrast ratio significantly higher than those in conventional imaging methods with and without PI. The results suggest that the 3P method is effective for specifically detecting microbubbles in cavitation-enhanced HIFU treatment.

show abstract

MRI guided and monitored focused ultrasound thermal ablation methods: a review of progress

Cited by 92 publications

References 47 publications

Pulsed-High Intensity Focused Ultrasound and Low Temperature–Sensitive Liposomes for Enhanced Targeted Drug Delivery and Antitumor Effect

Pulsed-High Intensity Focused Ultrasound and Low Temperature–Sensitive Liposomes for Enhanced Targeted Drug Delivery and Antitumor Effect

Driving delivery vehicles with ultrasound

Selective detection of cavitation bubbles by triplet pulse sequence in high-intensity focused ultrasound treatment

Contact Info

Product

Resources

About