Michael S Canney

University of Lyon, Lyons, Rhône-Alpes, France

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Publications (52)62.54 Total impact

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    ABSTRACT: Purpose: Glioblastoma is both the most common and aggressive primary brain tumor in adults. Carboplatin chemotherapy has shown only modest efficacy in progressive high-grade gliomas. The limited clinical efficacy of carboplatin may be due to its low concentration in tissue when the drug is delivered intravenously. The aim of this study was to assess whether the tissue concentration of intravenously administered carboplatin could be enhanced by ultrasound-induced blood-brain disruption in a primate model. Methods: Carboplatin was administered intravenously for 60 min to a single primate following blood-brain barrier opening induced by an implantable ultrasound device. Blood and brain samples were collected after animal killing, which occurred 60 min after the end of carboplatin administration. Platinum quantification in ultrafiltrate plasma and brain samples was performed using inductively coupled plasma mass spectrometry. Results: The brain concentration of platinum was highly enhanced (5.2×) in the 3.9 cm(3) region sonicated by the US beam, with a higher concentration in more vascularized anatomical structures. At 5 and 10 mm from the US beam axis, platinum concentrations were slightly enhanced (2.2× and 1.3× respectively). Conclusions: This study demonstrates that BBB opening using an implantable ultrasound transducer enhances the brain distribution of carboplatin in a loco-regional manner. Such a treatment approach is of significant interest for the treatment of primary brain tumors and is under current evaluation in a phase 1 clinical trial (NCT02253212).
    No preview · Article · Dec 2015 · Cancer Chemotherapy and Pharmacology
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    ABSTRACT: OBJECT The blood-brain barrier (BBB) limits the intracerebral penetration of drugs and brain tumor treatment efficacy. The effect of ultrasound-induced BBB opening on the intracerebral concentration of temozolomide (TMZ) and irinotecan (CPT-11) was assessed. METHODS This study was performed using 34 healthy New Zealand rabbits. Half had unilateral BBB opening, and half served as controls. Sonications were performed by pulsing a 1.05-MHz planar ultrasound transducer with a duty cycle of 2.5% and an in situ acoustic pressure level of 0.6 MPa after injection of a microbubble ultrasound contrast agent. Drugs were injected either 5 minutes before (ChemoPreUS) or 15 minutes after (ChemoPostUS) the ultrasound sonication. The plasma and intracerebral concentrations of both drugs were quantified using ultra-performance liquid chromatography. RESULTS The mean intracerebral tissue-to-plasma drug concentration ratio in the control hemispheres was 34% for TMZ and 2% for CPT-11. After BBB opening, these values increased by up to 21% for TMZ and up to 178% for CPT-11. Intracerebral concentrations of drugs were enhanced in regions where the BBB was opened compared with the contralateral hemisphere (p < 0.01 and p < 0.0001 for CPT-11, p = 0.02 and p = 0.03 for TMZ, in ChemoPreUS and ChemoPostUS, respectively) and compared with the control group (p < 0.001 and p < 0.0001 for CPT-11, p < 0.01 and p = 0.02 for TMZ, in ChemoPreUS and ChemoPostUS, respectively). The intracerebral distribution of drugs was heterogeneous, depending on the distance from the ultrasound source. CONCLUSIONS Ultrasound-induced opening of the BBB significantly enhances the intracerebral concentration of both TMZ and CPT-11 in rabbits.
    No preview · Article · Nov 2015 · Journal of Neurosurgery
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    Preview · Article · Jun 2015

  • No preview · Article · Nov 2014 · Neurochirurgie
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    ABSTRACT: Research on therapeutic ultrasound at LabTau (INSERM Lyon, France) began in the early 1980s with work on shock waves that lead to the development of the first ultrasound-guided lithotripter. In 1989, this research shifted towards new developments in the field of HIFU with applications in urology and oncology. The most significant developments have been obtained in urology with the Ablatherm™ project, a transrectal HIFU device for the thermal ablation of the prostate. This technology has since become an effective therapeutic alternative for patients with localized prostate cancer. Since 2000, three generations of the Ablatherm™ have been CE marked and commercialized by EDAP-TMS. The latest version, the FocalOne™, allows for the focal treatment of prostate cancer and combines dynamic focusing and fusion of MR images to ultrasound images acquired in real time by the imaging probe integrated in the HIFU transducer. Using toroidal ultrasound transducers, a HIFU device was also recently validated clinically for the treatment of liver metastases. Another novel application that has reached the clinic is for the treatment of glaucoma using a miniature, disposable HIFU device. Today, new approaches are also being investigated for treating cerebral and cardiac diseases.
    No preview · Article · Oct 2014 · The Journal of the Acoustical Society of America
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    ABSTRACT: Cavitation phenomena have been always considered as a predominant mechanism of concern in mechanical tissue damage induced by therapeutic ultrasound. Corresponding methods have been developed to monitor cavitation. Recently, a new high intensity focused ultrasound technology, called boiling histotripsy (BH), was introduced, in which the major physical phenomenon that initiates mechanical tissue damage is vapor bubble growth associated with rapid tissue heating to boiling temperatures. Caused by nonlinear propagation effects and the development of high-amplitude shocks, this tissue heating is localized in space and can lead to boiling within milliseconds. Once a boiling bubble is created, interaction of shock waves with the cavity results in tissue disintegration. While the incident shocks can lead to cavitation phenomena and accompanying broadband emissions, the presence of a millimeter-sized vapor cavity in tissue produces strong echogenicity in ultrasound (US) imaging that can be exploited with B-mode diagnostic ultrasound. Various other methods of imaging boiling histotripsy, including passive cavitation detection (PCD), Doppler or nonlinear pulse-inversion techniques, and high speed photography in transparent gel phantoms are also overviewed. The role of shock amplitude as a metric for mechanical tissue damage is discussed. [Work supported by NIH EB007643, T32DK007779, and NSBRI through NASA NCC 9-58.]
    No preview · Article · Oct 2014 · The Journal of the Acoustical Society of America
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    ABSTRACT: Interstitial thermal therapy is a minimally invasive treatment modality that has been used clinically for ablating both primary and secondary brain tumors. Here a multi-element interstitial ultrasound applicator is described that allows for increased spatial control during thermal ablation of tumors as compared to existing clinical devices. The device consists of an array of 56 ultrasound elements operating at 6 MHz, oriented on the seven faces of a 3.2 mm flexible catheter. The device was first characterized using the acoustic holography method to examine the functioning of the array. Then experiments were performed to measure heating in tissue-mimicking gel phantoms and ex vivo tissue samples using magnetic resonance imaging-based thermometry. Experimental measurements were compared with results obtained using numerical simulations. Last, simulations were performed to study the feasibility of using the device for thermal ablation in the brain. Experimental results show that the device can be used to induce a temperature rise of greater than 20 °C in ex vivo tissue samples and numerical simulations further demonstrate that tumors with diameters of greater than 30-mm could potentially be treated.
    No preview · Article · Aug 2013 · The Journal of the Acoustical Society of America
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    ABSTRACT: Object: The blood-brain barrier (BBB) is a major impediment to the intracerebral diffusion of drugs used in the treatment of gliomas. Previous studies have demonstrated that pulsed focused ultrasound (US) in conjunction with a microbubble contrast agent can be used to open the BBB. To apply the US-induced opening of the BBB in clinical practice, the authors designed an innovative unfocused US device that can be implanted in the skull and used to transiently and repeatedly open the BBB during a standard chemotherapy protocol. The goal of this preliminary work was to study the opening of the BBB induced by the authors' small unfocused US transducer and to evaluate the effects of the sonications on brain parenchyma. Methods: Craniectomy was performed in 16 healthy New Zealand White rabbits; epidural application of a single-element planar ultrasonic transducer operating at 1 MHz was then used with a pulse-repetition frequency of 1 Hz, pulse lengths of 10-35 msec, in situ acoustic pressure levels of 0.3-0.8 MPa, and sonication for 60-120 seconds. SonoVue was intravenously injected during the US applications, and opening of the BBB was determined by detecting extravasation of Evans blue dye (EBD) in brain tissues, quantitative measurement of EBD with UV-visible spectrophotometry, and contrast enhancement after Gd injection in 4.7-T MRI. A histological study was performed to determine adverse effects. Results: An opening of the BBB was observed over a large extent of the US beam in the brain corresponding to in situ pressures of greater than 0.2 MPa. The BBB opening observed was highly significant for both EBD (p < 0.01) and MRI Gd enhancement (p < 0.0001). The BBB opening was associated with minor adverse effects that included perivascular red blood cell extravasations that were less than 150 μm in size and not visible on MR images. Moderate edema was visible on FLAIR sequences and limited to the extent of the sonication field. Conclusions: The results demonstrate that the BBB can be opened in large areas of the brain in rabbits with low-power, pulsed, and unfocused US with limited damage to healthy tissue.
    No preview · Article · Jun 2013 · Journal of Neurosurgery
  • Moath M Al-Qraini · Michael S Canney · Ghanem F Oweis
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    ABSTRACT: Free field experimental measurements of the temperature rise of water in the focal region of a 2 MHz high intensity focused ultrasound (HIFU) transducer were performed. The transducer was operated in pulse-mode with millisecond bursts, at acoustic intensities of 5 to 18.5 kW/cm(2) at the focus, resulting in non-linear wave propagation and shock wave formation. Pulsed, planar, laser-induced fluorescence (LIF) was used as a fast rise-time, non-intrusive, temperature measurement method of the water present in the focal region. LIF thermometry is based on calibrating the temperature-dependent fluorescence intensity signal emitted by a passive dye dissolved in water when excited by a pulse of laser light. The laser beam was formed into a thin light sheet to illuminate a planar area in the HIFU focal region. The laser light sheet was oriented transverse to the acoustic axis. Cross-sectional, instantaneous temperature field measurements within the HIFU focal volume showed that the water temperature increased steadily with increasing HIFU drive voltage. Heating rates of 4000-7000°C/s were measured within the first millisecond of the HIFU burst. Increasing the length of the burst initially resulted in an increase in the water temperature within the HIFU focal spot (up to ∼3 ms), after which it steadied or slightly dropped. Acoustic streaming was measured and shown to be consistent with the reduction in heating with increased burst length due to convective cooling. LIF thermometry may thus be a viable non-invasive method for the characterization of HIFU transducers at high power intensities.
    No preview · Article · Apr 2013 · Ultrasound in medicine & biology

  • No preview · Article · Dec 2012 · Neurochirurgie
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    ABSTRACT: In this work, a new therapeutic ultrasound device is presented that is designed for performing minimally invasive thermal ablation of brain tumors under guidance with magnetic resonance imaging (MRI). The device consists of an array of ultrasound transducers, oriented on multiple faces of a flexible sheath with an integrated cooling system that can be directly inserted into the brain through a small burr hole in the skull. Heating can be monitored using real-time MRI and conformed to the tumor volume by varying the power to the individual elements on the probe. In this work, preliminary testing of the device was performed and included acoustic characterization, numerical simulations, and experiments in a clinical MRI system. Numerical simulations of the acoustic field and temperature rise during heating were compared with results of in vitro testing using bovine brain samples. The results demonstrate that the device has good MRI compatibility and is capable of generating output surface intensities of greater than 20 W/cm2, which is sufficient to ablate tissue at depths of more than 10 mm from the probe in less than four minutes of heating.
    No preview · Article · Oct 2012
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    ABSTRACT: In this paper, multi-element arrays based on cMUT and piezoelectric technologies, using the same geometry, have been realized. The first part of the paper is focused on comparing both in terms of imaging performances. The CMUT is shown to be lower in sensivity but better in terms of bandwidth and resolution. The second part of the paper investigates the ability of the CMUT array for HIFU applications. The dual imaging-HIFU capability of the cMUT array is demonstrated. This is a new feature of the CMUT technology, as piezoelectric transducers are designed with a trade-off between bandwidth and transduction efficiency.
    No preview · Conference Paper · Oct 2012
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    Preview · Article · Apr 2012
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    Preview · Article · Apr 2012
  • Kevin Beccaria · Michael S. Canney · Alexandre C. Carpentier
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    ABSTRACT: Lasers were invented in the middle of the 20th century, from the previous theoretical work of Einstein on the process of amplification of stimulated emission, and quickly became used in various devices for industrial, telecommunication and military applications. In the medical field, neurosurgeons were some of the first researchers to investigate the use of lasers for therapy in the 1960s, but were limited by cumbersome designs and the availability of lasers that could only operate in pulsed modes. As improved laser designs were introduced that allowed for continuous mode operation and other wavelengths, new medical techniques were developed and improved. Subsequently, in the early 1970s, Sutton introduced the concept of interstitial hyperthermia, which led to the development of a new technique called laser interstitial thermotherapy (LITT). LITT treatments consist of heating tumors with prolonged and moderate temperature elevations, inducing alteration of cell membranes and enzyme denaturation, leading to the formation of a selective zone of coagulation necrosis in the heated tissue without vaporization. The Nd-YAG and diode laser are the most frequent lasers used for LITT due to their optimum wavelength for absorption and heating in tissue. With the recent development and widespread availability of magnetic resonance imaging (MRI), laser fibers can be inserted stereotactically within the tumor and the treatment can be controlled in real-time. MR imaging allows for monitoring of the temperature elevation in the treated area and for prediction of the extent of induced necrosis based on the temperature history. Several clinical studies have been performed that show that the technique is now safe and allows for control of brain tumors metastases for which traditional treatments including radiosurgery have failed. Additional technical progress is now being performed on methods to treat tumors with larger diameters and with more complex shapes. Lastly, additional clinical studies are needed in larger patient populations to confirm the findings of the initial clinical trials.
    No preview · Chapter · Jan 2012
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    ABSTRACT: In high intensity focused ultrasound (HIFU) applications, tissue may be thermally necrosed by heating, emulsified by cavitation, or, as was recently discovered, emulsified using repetitive millisecond boiling caused by shock wave heating. Here, this last approach was further investigated. Experiments were performed in transparent gels and ex vivo bovine heart tissue using 1, 2, and 3 MHz focused transducers and different pulsing schemes in which the pressure, duty factor, and pulse duration were varied. A previously developed derating procedure to determine in situ shock amplitudes and the time-to-boil was refined. Treatments were monitored using B-mode ultrasound. Both inertial cavitation and boiling were observed during exposures, but emulsification occurred only when shocks and boiling were present. Emulsified lesions without thermal denaturation were produced with shock amplitudes sufficient to induce boiling in less than 20 ms, duty factors of less than 0.02, and pulse lengths shorter than 30 ms. Higher duty factors or longer pulses produced varying degrees of thermal denaturation combined with mechanical emulsification. Larger lesions were obtained using lower ultrasound frequencies. The results show that shock wave heating and millisecond boiling is an effective and reliable way to emulsify tissue while monitoring the treatment with ultrasound.
    Full-text · Article · Nov 2011 · The Journal of the Acoustical Society of America

  • No preview · Article · Sep 2011 · Neurochirurgie
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    ABSTRACT: Recent studies in high intensity focused ultrasound (HIFU) have shown significant interest in generating purely mechanical damage of tissue without thermal coagulation. Here, an approach using millisecond bursts of ultrasoundshock waves and repeated localized boiling is presented. In HIFU fields, nonlinear propagation effects lead to formation of shocks only in a small focal region. Significant enhancement of heating due to absorption at the shocks leads to boiling temperatures in tissue in milliseconds as calculated based on weak shock theory. The heated and potentially necrotized region of tissue is small compared to the volume occupied by the mm‐sized boiling bubble it creates. If the HIFU pulse is only slightly longer than the time‐to‐boil, thermal injury is negligible compared to the mechanical injury caused by the exploding boiling bubble and its further interaction with shocks. Experiments performed in transparent gels and various ex vivo and in vivo tissues have confirmed the effectiveness of this emulsification method. In addition, since mm‐sized boiling bubbles are highly echogenic, tissue emulsification can be easily monitored in real‐time using B‐mode ultrasound imaging. [Work supported by NIH EB007643, RFBR 09‐02‐01530, and NSBRI through NASA NCC 9‐58].
    No preview · Article · Apr 2011 · The Journal of the Acoustical Society of America

  • No preview · Article · Jan 2011 · Medical Physics
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    ABSTRACT: Conventional treatments for cerebral tumors involve surgical resection of the lesion in combination with chemotherapy or radiotherapy. In this work, an alternative, minimally invasive approach is presented for thermally ablating cerebral tumors using an interstitial ultrasound transducer. Initial testing and characterization of a prototype device based on a mono-element design is presented. Heating experiments are performed in tissue phantoms and in ex vivo bovine and sheep brain. Real-time temperature monitoring and lesion characterization are performed using magnetic resonance imaging (MRI). Furthermore, obtained temperature rise and lesion volume registered on MRI are compared with numerical modeling. The results demonstrate that the prototype interstitial probes have good MRI compatibility and are capable of ablating a volume of tissue of up to several centimeters in diameter in several minutes under real-time MRI guidance. Furthermore, there is a possibility to precisely tailor the lesion volume to the treatment zone using a rotational approach. [Work supported by the ASA Hunt Fellowship and CarThéra SAS.].
    No preview · Article · Oct 2010 · The Journal of the Acoustical Society of America

Publication Stats

334 Citations
62.54 Total Impact Points


  • 2013
    • University of Lyon
      Lyons, Rhône-Alpes, France
    • Hôpitaux Universitaires La Pitié salpêtrière - Charles Foix
      Lutetia Parisorum, Île-de-France, France
  • 2012
    • Hôpital La Pitié Salpêtrière (Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix")
      Lutetia Parisorum, Île-de-France, France
  • 2011-2012
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2006-2010
    • University of Washington Seattle
      • Applied Physics Laboratory
      Seattle, Washington, United States
  • 2008
    • Trinity Washington University
      Washington, Washington, D.C., United States