Mechanical fractionation of tissues using microsecond-long HIFU pulses on a clinical MR-HIFU system

Eranki, Avinash; Farr, Navid; Partanen, Ari; Sharma, Karun; Rossi, Christopher T.; Rosenberg, Avi Z.; Kim, AeRang; Oetgen, Matthew E.; Çelik, Haydar; Woods, David L.; Yarmolenko, Pavel S.; Kim, Peter C.W.; Wood, Bradford J.

doi:10.1080/02656736.2018.1438672

Cited by 26 publications

(16 citation statements)

References 57 publications

(83 reference statements)

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“…The role of FUS in the tumor microenvironment remains to be elucidated for this study. FUS treatment, by itself or in combination with MBs, causes mechanical fractionation of the tumor tissues at the focal point and triggers the release of tumor antigens to the microenvironment [ 43 ]. Enhanced tumor antigen release potentiates dendritic cell maturation, which in turn triggers priming of the T cells and immunological responses against the tumor cells [ 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

PD-L1 Targeting Immune-Microbubble Complex Enhances Therapeutic Index in Murine Colon Cancer Models

Kim

Lee²,

Moon³

et al. 2020

Pharmaceuticals

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Cancer immunotherapy has revolutionized the way different neoplasms are treated. Among the different variations of cancer immunotherapy, the checkpoint inhibitors targeting the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis have been validated and are currently used in the clinics. Nevertheless, these therapeutic antibodies are associated with significant side effects and are known to induce immune-related toxicities. To address these issues, we have developed an immune-microbubble complex (IMC) which not only reduces the toxicities associated with the antibodies but also enhances the therapeutic efficacy when combined with focused ultrasound. The concept of IMCs could be applied to any type of antibody-based treatment regimens to maximize their therapeutic potential.

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Section: Discussionmentioning

confidence: 99%

PD-L1 Targeting Immune-Microbubble Complex Enhances Therapeutic Index in Murine Colon Cancer Models

Kim

Lee²,

Moon³

et al. 2020

Pharmaceuticals

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“…Additionally, we performed pulsed boiling histotripsy (BH) sonications using acoustic power of 450 W, 10 ms long pulses, and 30 pulses per trajectory point. BH is a HIFU technique that is capable of precise mechanical fractionation of target tissue with minimal surrounding heating [2, 3, 37]. Furthermore, as representative examples, HIFU sonications were performed in TMTCP embedded with either a rubber blood vessel -mimic with water flow, or plastic rib mimic (VeroWhitePlus, Stratasys, Ltd., MN, USA; acoustic attenuation = 3.0 dB/cm @ 1 MHz, speed of sound = 2539 m/s) [38].…”

Section: Methodsmentioning

confidence: 99%

“…High intensity focused ultrasound (HIFU) is a therapeutic modality useful for a wide variety of clinical applications, and is capable of non-invasive, volumetric tissue heating to induce targeted and localized thermal ablation, mild hyperthermia, and/or mechanical fractionation [1, 2, 3, 4]. HIFU is generally performed under magnetic resonance imaging (MR-HIFU) or ultrasound imaging (US-HIFU) guidance [5, 6, 7, 8, 9].…”

Section: Introductionmentioning

confidence: 99%

Tissue-mimicking thermochromic phantom for characterization of HIFU devices and applications

Eranki

Mikhail

Negussie

et al. 2019

International Journal of Hyperthermia

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Purpose: Tissue-mimicking phantoms (TMPs) are synthetic materials designed to replicate properties of biological tissues. There is a need to quantify temperature changes following ultrasound or magnetic resonance imaging-guided high intensity focused ultrasound (MR-HIFU). This work describes development, characterization, and evaluation of tissue-mimicking thermochromic phantom (TMTCP) for direct visualization and quantification of HIFU heating. The objectives were to 1) develop an MR-imageable, HIFU-compatible TMTCP that reports absolute temperatures, 2) characterize TMTCP physical properties, and 3) examine TMTCP color change after HIFU. Methods and Materials: A TMTCP was prepared containing thermochromic ink, silicon dioxide, and bovine serum albumin and its properties were quantified. A clinical MRI-guided and a preclinical US-guided HIFU system were used to perform sonications in TMTCP. MRI thermometry was performed during HIFU, followed by T2-weighted MRI post-HIFU. Locations of color and signal intensity change were compared to the sonication plan and to MRI temperature maps. Results: TMTCP properties were comparable to those in human soft tissues. Upon heating, the TMTCP exhibited an incremental but permanent color change for temperatures between 45 and 70°C. For HIFU sonications the TMTCP revealed spatially sharp regions of color change at the target locations, correlating with MRI thermometry and hypointense regions on T2-weighted MRI. TMTCP-based assessment of various HIFU applications was also demonstrated. Conclusion: We developed a novel MR-imageable and HIFU-compatible TMTCP to characterize HIFU heating without MRI or thermocouples. The HIFU-optimized TMTCP reports absolute temperatures and ablation zone geometry with high spatial resolution. Consequently, the TMTCP can be used to evaluate HIFU heating and may provide an in vitro tool for peak temperature assessment, and reduce preclinical in vivo requirements for clinical translation.

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“…High-intensity focused ultrasound (HIFU) is a non-invasive therapy that is used in the clinic to thermally ablate solid tumors with high spatial precision, 74 and to mechanically disrupt tumors. 75 HIFU-mediated tumor fractionation may cause ICD and increase inflammation 76 and potentially lead to immune sensitisation. 77 Eranki et al 78 recently demonstrated a combination of HIFU and ICI significantly enhanced systemic antitumor responses and cured the majority of mice with large, established unilateral and bilateral neuroblastoma tumors.…”

Section: Conventional Cancer Therapiesmentioning

confidence: 99%

“…These data provide a promising alternative to transform a 'cold' tumor into a 'hot' one. High‐intensity focused ultrasound (HIFU) is a non‐invasive therapy that is used in the clinic to thermally ablate solid tumors with high spatial precision, 74 and to mechanically disrupt tumors 75 . HIFU‐mediated tumor fractionation may cause ICD and increase inflammation 76 and potentially lead to immune sensitisation 77 .…”

Section: Inducing Immunogenic Tumor Cell Death (Icd)mentioning

confidence: 99%

Therapeutic strategies to remodel immunologically cold tumors

Wang

Desai

et al. 2020

Clin & Trans Imm

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Immune checkpoint inhibitors (ICIs) induce a durable response in a wide range of tumor types, but only a minority of patients outside these ‘responsive’ tumor types respond, with some totally resistant. The primary predictor of intrinsic immune resistance to ICIs is the complete or near‐complete absence of lymphocytes from the tumor, so‐called immunologically cold tumors. Here, we propose two broad approaches to convert ‘cold’ tumors into ‘hot’ tumors. The first is to induce immunogenic tumor cell death, through the use of oncolytic viruses or bacteria, conventional cancer therapies (e.g. chemotherapy or radiation therapy) or small molecule drugs. The second approach is to target the tumor microenvironment, and covers diverse options such as depleting immune suppressive cells; inhibiting transforming growth factor‐beta; remodelling the tumor vasculature or hypoxic environment; strengthening the infiltration and activation of antigen‐presenting cells and/or effector T cells in the tumor microenvironment with immune modulators; and enhancing immunogenicity through personalised cancer vaccines. Strategies that successfully modify cold tumors to overcome their resistance to ICIs represent mechanistically driven approaches that will ultimately result in rational combination therapies to extend the clinical benefits of immunotherapy to a broader cancer cohort.

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Mechanical fractionation of tissues using microsecond-long HIFU pulses on a clinical MR-HIFU system

Cited by 26 publications

References 57 publications

PD-L1 Targeting Immune-Microbubble Complex Enhances Therapeutic Index in Murine Colon Cancer Models

PD-L1 Targeting Immune-Microbubble Complex Enhances Therapeutic Index in Murine Colon Cancer Models

Tissue-mimicking thermochromic phantom for characterization of HIFU devices and applications

Therapeutic strategies to remodel immunologically cold tumors

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