This present invention pertains to an interventional photoacoustic imaging system. More particularly the present invention pertains to an interventional photoacoustic imaging system useful for imaging during cancer treatments for the prostate, liver and the like.
Prostate cancer is the leading form of cancer in men in the U.S. For several decades, the definitive treatment for low and medium risk prostate cancer was radical prostatectomy or external beam radiation therapy. More recently, low dose rate (LDR) permanent seed brachytherapy has been used to achieve equivalent outcomes. Brachytherapy is a form of cancer treatment where a radiation source, in the form of radioactive seeds, is positioned at or near the site requiring treatment. For treatment of prostate cancer, brachytherapy seeds are implanted in the tumor and left there to decay over time. Over a period of a few weeks or so, the level of radiation emitted by such seeds will decline to almost zero.
Brachytherapy accounts for a significant and growing proportion of prostate cancer treatments, as it is delivered with minimal invasiveness in an outpatient setting. Brachytherapy is mostly performed with transrectal ultrasound (TRUS) guidance. While TRUS provides adequate imaging of the soft tissue anatomy, it does not allow for localization or precise placement of the implanted brachytherapy seeds, which is a major technical limitation of contemporary brachytherapy. Faulty needle and seed placement often causes insufficient dosing to the cancer site and/or inadvertent radiation of the rectum, urethra, and bladder. The former causes failure of treatment, while the latter results in adverse side effects like rectal ulceration, incontinence, and impotence.
Algorithmic and computational tools are available to optimize a brachytherapy treatment plan intra-operatively. Implant planning is based on idealistic pre-planned seed patterns. These methods, however, critically require that the exact 3-dimensional locations of the implanted seeds are precisely known with respect to the patient's anatomy. Transrectal ultrasound is insufficient for visualizing the seeds within the patient's anatomy.
To provide more accurate imaging, other techniques have emerged. For example, more advanced ultrasound image processing, which incorporate additional modalities like X-rays, have emerged. The use of magnetic resonance imaging has also gained acceptance. However, none of the proposed solutions is effective, simple to use, and low in cost.
Prior to the newer techniques, CT imaging was the only reliable modality to determine if the seeds were implanted at appropriate positions. However, CT imaging is typically acquired weeks after the procedure when edema has subsided. Accordingly, there may cold spots (i.e. under-dosed areas) left in prostate at the end of the procedure. Without having the means of any true quantitative intra-operative dosimetry, these cold spots are left untreated and lead to an increased probability of treatment failure.
In addition to brachytherapy, ablation is also used to treat prostate cancer and the like. In spite of promising results of ablative therapies, significant technical barriers exist with regard to its efficacy, safety, and applicability to many patients. Specifically, these limitations include: (1) localization/targeting of the tumor and (2) monitoring of the ablation zone.
One common feature of current ablative methodology is the necessity for precise placement of the end-effector tip in specific locations, typically within the volumetric center of the tumor, in order to achieve adequate destruction. The tumor and zone of surrounding normal parenchyma can then be ablated. Tumors are identified by preoperative imaging, primarily CT and MR, and then operatively (or laparoscopically) localized by intra-operative ultrasonography (IOUS). When performed percutaneously, trans-abdominal ultrasonography is most commonly used. Current methodology requires visual comparison of preoperative diagnostic imaging with real-time procedural imaging, often requiring subjective comparison of cross-sectional imaging to IOUS. Then, manual free-hand IOUS is employed in conjunction with free-hand positioning of the tissue ablator under ultrasound guidance.
In addition, target motion upon insertion of the ablation probe makes it difficult to localize appropriate placement of the therapy device with simultaneous target imaging. The major limitation of ablative approaches is the lack of accuracy in probe localization within the center of the tumor. In addition, manual guidance often requires multiple passes and repositioning of the ablator tip, further increasing the risk of bleeding and tumor dissemination. In situations when the desired target zone is larger than the single ablation size (e.g. 5-cm tumor and 4-cm ablation device), multiple overlapping spheres are required in order to achieve complete tumor destruction. In such cases, the capacity to accurately plan multiple manual ablations is significantly impaired by the complex 3-dimensional geometrically complex planning required as well as image distortion artifacts from the first ablation, further reducing the targeting confidence and potential efficacy of the therapy. Current monitoring approaches often result in either local failure or in excessively large zones of liver ablation.
Recently, photoacoustic imaging has emerged as a promising new medical imaging modality suitable for various structural, functional, and molecular imaging applications. It is based upon the principle of the photoacoustic effect, simply defined as a physical phenomenon of the conversion of light waves to sound waves depending on a tissue's optical properties. Therefore, photoacoustic imaging involves the detection of sound waves as is also done in ultrasound. In contrast, while ultrasound detects sound waves resulting from scatters or reflections of emitted sound, photoacoustic imaging detects sound waves resulting from the photoacoustic effect generated by a light source (e.g, a laser). However, there has yet been a photoacoustic imaging method and system that provides an integrative and cost effective way to image in real time during cancer treatment, particularly during brachytherapy.
Accordingly, there is a need in the art for a more effective imaging method and system that allows an area under cancer treatment to be imaged in real time.
According to a first aspect of the present invention, an interventional photoacoustic imaging system for cancer treatment comprises an energy source including an optical source for applying laser energy to optically excite a treatment area, a device for inserting the optical source into a body of a patient adjacent the treatment area, an ultrasonic transducer for detecting the acoustic waves, and a processor for analyzing the acoustic waves to thereby form a photoacoustic image of the tissue in real time. It is understood that the excitation of sound in a condensed medium is produced by penetrating radiation (beams of protons, electrons, photons, etc.), that is both modulated in intensity and pulsed.
According to a second aspect of the present invention, an interventional photoacoustic imaging method comprises inserting an ultrasonic transducer into a body of a patient, inserting an energy source including an optical source into the body of the patient adjacent a treatment area, illuminating the treatment area with the optical source, detecting acoustic signals generated in the treatment area with the ultrasonic transducer, and analyzing the detected acoustic signals to generate a photoacoustically image of the treatment area.
According to a third aspect of the present invention, a method of imaging implanted brachytherapy seeds comprises implanting a brachytherapy seed into a treatment area. An energy source including an optical source is applied to the treatment area causing the brachytherapy seed to expand and generate acoustic signals. The acoustic signals are detected with an ultrasonic transducer, and are analyzed to generate a photoacoustic image of the seed.
The accompanying drawings provide visual representations which will be used to more fully describe the representative embodiments disclosed herein and can be used by those skilled in the art to better understand them and their inherent advantages. In these drawings, like reference numerals identify corresponding elements and:
a) is a photograph of a one-seed phantom.
b) is a songraphic image in B-mode of the one-seed phantom.
c) is a photoacoustic image of the one-seed phantom before beamforming.
d) is a photoacoustic image of the one-seed phantom after beamforming according to features of the present invention.
a) is a photograph of a four-seed phantom.
b) is a songraphic image in B-mode of the four-seed phantom.
c) is a photoacoustic image of the four-seed phantom before beamforming.
d) is a photoacoustic image of the four-seed phantom after beamforming according to features of the present invention.
a) is a photograph of a dog prostate phantom.
b) is a songraphic image in B-mode of the dog prostate phantom.
c) is a photoacoustic image of the dog prostate phantom before beamforming.
d) is a photoacoustic image of the dog prostate phantom after beamforming according to features of the present invention.
The present invention pertains to an interventional photoacoustic imaging system that may be incorporated into pre-existing medical devices used for treatment of cancer. In particular, a system is developed to allow for photoacoustic imaging of the prostate (or other organ) during cancer treatment, such as hrachytherapy treatment or ablation therapy. In these treatments, precise imaging of the prostate and cancerous tissue, as well as the seeds, is imperative so that effective treatment may be rendered. However, it should be understood that the photoacoustic imaging system and method of the present invention may also be used during laparoscopic surgery, open surgery, and/or natural orifice translumenal surgery (NOTES).
The present invention provides for visualization of the prostate anatomy in real time so that cancer treatments may be rendered effectively in the treatment area of a patient. For example, molecular imaging of the prostate is possible, including edema characterization and mapping radiation dose to actual cancer locations. The present invention also allows for effective imaging of the brachytherapy seeds during the treatment, to thereby verify the proper positioning of the seeds within the prostate according to the treatment plan. Finally, the photoacoustic imaging method and system may be used as an ablation therapy by depositing high laser energy that can cause selective cell necrosis. As used herein, brachytherapy seeds, which are well known, are radioactive sources that are locally deployed adjacent to or implanted within a cancerous site. While brachytherapy seeds are specifically identified, it should be understood that other types of therapeutic seeds may be used in accordance with features of the present invention.
With reference to
As shown in
According to known principles, acoustic signals may be acquired by the processor 13, and stored in the memory device 14. The memory device 14 may include one or more computer readable storage media, as well as machine readable instructions for performing processing necessary to form B-mode images. Once the B-mode images are processed, they are displayed on the interface 15, as is known in the art. One skilled in the art will readily appreciate that many variations to ultrasonic system 11 are possible and within the scope of the invention. For example, the ultrasonic system 11 may be a 2-dimensional or 3-dimensional system, but other systems are possible depending on application and design preference.
As is known in the art, a pre-operative treatment plan is generated or the placement of the brachytherapy seeds into the cancerous organ or ablation of the particular area. When performing brachytherapy or ablation therapy, a perineum template may be used to guide the particular needles into the predetermined location. In this regard, a template fixture 20 is used to support a perineum template 22. An example of a perineum template is described in U.S. Pat. No. 6,579,262, the entire disclosure of which is incorporated by reference herein. The perineum template 22 includes a grid of needles holes (not shown) which serve to guide one or more brachytherapy needles or biopsy needles 24 into the treatment area of the patient, for example (and as shown in
Typically, B-mode ultrasonic images generated from the transrectal probe 12 are the choice modality for imaging the prostate prior to treatment. However, while ultrasonic images provide adequate imaging of the soil tissue anatomy, they do not allow for localization of the implanted brachytherapy seeds.
With further reference to
Preferably, a separate computer system 29 is provided to processes the raw data and form photoacoustic images. That is, raw data may be streamed in parallel fashion to the separate processor 29, so that the data may be processed therein to form a photoacoustic image. In this way, the computer system 29 has a memory device 31 including machine readable instructions for performing photoacoustic imaging. Once the photoacoustic images are formed, they may be displayed on an interface 33.
Alternatively, the photoacoustic image may be formed in processor 13 by memory 14. In this way, memory 14 may include additional machine readable instructions to form the photoacoustic image. The photoacoustic images may then be redirected to interface 15, where multiple images may be displayed thereon.
As shown in
To transmit laser energy to the treatment area, a laser 40 is connected to optical fiber 30. The laser 40, which is controlled by laser controller 42, is preferably a fiber laser capable of generating short pulses of light. The use of fiber lasers and fiber-based components eliminates the need for alignment and makes the whole system rugged, compact, and light. However, any other type of laser system may be incorporated, according to application and design preference.
As shown in
For example, with reference to
To image the tissue of the prostate 18, the optical fiber 30 may be advanced at various locations along the urethra 38. That is, optical fiber 30 and accompanying laser source may not be sufficiently strong to generate wavelengths throughout the entire volume of the prostate at a single location. Accordingly, the optical fiber 30 may be positioned at different locations along the urethra 38, so that the entire prostate 18 may be imaged. As such, acquisition of imaging data of the entire prostate may be effected. To facilitate tracking of the catheter 39 in the prostate, sensors, such as electromagnetic sensors, may be attached to the catheter 39, and are tracked by electromagnetic tracking systems (which may be placed under the patient). Photoacoustic phenomenon can also be used to enable tracking of the beam. For example, instead of using 1064 nm wavelength, our system can alternate to 532 nm which is highly absorbed by tissues and will have smaller penetration depth. As such, the system can alternate between 1064 nm wavelength (to image seeds), and 532 nm (to detect the location of the beam).
Preoperatively and postoperatively, insertion of the optical fiber through the urethra 38 may be a preferred method of insertion as a catheter causes lesser trauma than insertion of needles. However, during the interventional operation, where needles are being inserted according to a preoperative plan, the optical fiber coupled to the needle will allow for frequent and instantaneous imaging adjacent the area to be treated. Nevertheless, both methodologies allow for real time imaging of the prostate and to verify that ablation or seed implantation has occurred at their targeted locations, which may eliminate the need for costly and potentially dangerous CT scans.
In addition, thermal imaging may be performed on the prostate 18. In particular, thermal imaging software may be integrated into processor 13 to track temperature elevations within +/−½ degrees C. In particular, the allowed FDA limit for energy flux (30 mJ/cm2) can potentially elevate the temperature of the irradiated area by a half degree depending on the amount of energy, absorption and laser flux profile. Thermal imaging technology can be used to monitor laser energy deposition. Thermal imaging may also be helpful to track the laser source as it moves during the procedure.
For example, thermal imaging may be used as a quality control to monitor the deposited laser energy. For example, with reference to
In addition, thermal imaging can be used to monitor ablation therapy. With reference to
As described above, an optical fiber may be used for ablation itself. In particular, the laser system can be designed to deliver laser energy at a sufficient level for ablation. As such, the optical fiber could serve dual purposes of photoacoustic imaging as well as performing ablation of the cancerous tissue. For example, U.S. Patent Publication No. 2010/0028261, the entire disclosure of which is incorporated by reference herein, relates to molecular specific photoacoustic imaging. By using gold nano particulars to identify cancer markers or contrast agents, the interventional photoacoustic imaging system 10 of the present invention can be tuned (i.e., tune the laser pulse to a specific wavelength, which has maximum absorption by these nano-tubes and minimal interactions with surrounding tissues) to specifically target those gold nano particulars, hence providing molecular imaging. By increasing the laser energy, the high photon counts will cause local ablation only at the region with high absorption (where the tumor markers are located).
Prior to operating the interventional photoacoustic imaging system 10 of the present invention, the optimum laser beam parameters for a particular treatment should be determined. The laser beam parameters will depend upon the optical properties of the treatment area, including the cancerous and normal tissue, as well as any seed that may be implanted therein. The laser beam parameters should be chosen for maximum tissue penetration while minimizing tissue damage. Mainly due to the water and hemoglobin content of tissue, the optical penetration depth of tissue can vary significantly even within tens of nanometers difference in optical wavelength.
In this regard, a laser that has broad wavelength tunability should be used. An example of such a laser is a Ytterbium doped fiber laser (Yb-FL). The Yb-FL laser is capable of generating high energy nanosecond pulses and capable of efficiently fiber optically delivering the beam to the tissue.
In the present invention, it was discovered that when imaging the tissue and edema, the wavelength of the laser energy should be in the range of between about 700 nm and 1350 nm depending on the resolution and the depth of imaging. For the imaging of the metal brachytherapy seeds in the tissue, the wavelength of the laser energy also should be in the range of about 700 nm to 1350 nm. The particular wavelength chosen will depend on the type of imaging that is desired.
It is also important to understand the photoacoustic properties of the tissue as well as the seeds when designing a system for generating photoacoustic images. With reference to
As shown in
An experimental system was developed to determine, through photoacoustic imaging, seed location in several test phantoms implanted with brachytherapy seeds. During the experiment, pulsed laser light from a Nd:YAG (neodymium-doped yttrium aluminum garnet) laser was directed towards the phantoms. Due to the intense nature of the generated laser beam, it was necessary to reduce the beam intensity. This was achieved through the use of 2, 45° dielectric mirrors, two black holes (to absorb the laser beam), and an adjustable aperture. The beam was passed through the first 45° dielectric mirror with a significant portion of the beam being deflected into the first black bole. This process was repeated and the resultant beam was passed through an adjustable aperture to further modify beam intensity. As such, the beam intensity could be adjusted to a value of approximately 10 mJ/cm2.
The phantoms used were made of two layers having different optical absorption coefficients (similar to the embedded metallic seed in tissue). Specifically, the phantoms were made of polyvinyl chloride-plastisol (PVCP), which mimicked the optoacoustic properties of tissue. The phantom layers were made of PVCP (white) and black plastic color. The optical properties of the phantom could be changed by varying the concentration of PVCP used to prepare it. The white portion was opaque and does not absorb light at 1064 nm. Therefore, the lack of absorption of light at the 1064 nm wavelength allowed the response of the brachytherapy seeds to be observed. Two seeds were implanted into the phantom at a distance of 5 mm apart.
A linear transducer array of 128 elements (used in conjunction with the Ultrasonix open US platform) was positioned adjacent the tissue phantom (using a coupling gel) to create B-mode images and photoacoustic images of two brachytherapy seeds. As shown in
With reference to
The laser 100 was incorporated into ultrasound system 102. The ultrasound system 102, including transducer 103, was used to detect sound waves generated by the photoacoustic effect. In particular, the ultrasound system 103 was an ultrasonic open research platform known as SONIXCEP manufactured by Ultrasonix Medical Corporation (“Ultrasonic”) located in Richmond, BC, Canada. For faster acquisition, a separately developed data acquisition hardware (DAQ) 104 known as SonixDAQ was connected to the ultrasound system 102 to allow raw pre-beamformed data in parallel to be acquired. That is, as described above, the acquired echos were streamed to a separate processor or processing area before beamforming occurred. In particular, the particular SonixDAQ module 104 used in the experiment supports data acquisition from 128 elements with 12-bit sampling along the external triggering for synchronous data acquisition. In addition, the SonixDAQ has a 16 GB internal memory, a 40 MHz internal clock, and a USB port for transferring data.
To read the raw radio frequency (RF) pre-beamformed data from the SonixDAQ and produce B-mode photoacoustic images, software 106 developed by Ultrasonix (i.e., DAQControl Software) was used. After the raw RF pre-formed data was read from the software 106, a script 108 was implemented to process the RF data into pre-beamformed and standard delay-and-sum B-mode images. Preferably, the software 106 and script 108 are included in the data acquisition hardware (DAQ) 104. However, it should be understood that they may be run in one or more separate processors. In addition, standard ultrasound software 110 is provided for operating the transducer 103, for example, SonixRP Software developed by Ultrasonix. Preferably, the software 110 is run in a processor included the ultrasound system 102.
With reference to
a) show a photograph of the one-seed phantom,
To further optimize the photoacoustic image, the ultrasonic system including the beamforming sequence for the linear array may be synchronized with the pulsed laser energy. In this way, laser parameters stored in the laser controller 42 may be acquired by the processor 29 (shown in
With reference to
Once the needle 24 (or ablation tool 150 or catheter 39) is positioned either adjacent and within the prostate 18, the pulsed laser energy is sent through the optical fiber 30, thereby illuminating the neighboring areas. The pulsed laser energy is absorbed by the prostate 18, thereby generating acoustic signals which propagate towards the transrectal probe 12. The signals received in the transrectal probe 12 are acquired by the processor 29 (or processor 13) and analyzed therein. As described with reference to
Imaging of the seeds 26 is performed similar to imaging of the prostate 18, as described above. In particular, the transrectal probe 12 is positioned in the rectum 16 such that the prostate 18 is in it imaging view. An optical fiber 30 coupled with a needle 24 (or ablation tool 150 as shown in
As is known in the art, the needle 24 functions to deliver seeds 26 into predetermined locations. In addition, the needle 24 provides pulsed laser towards the seeds 26, so that embedded seeds 26 may be imaged. Preferably, the pulsed laser energy is about 1064 nm, so that only the seeds are imaged. However, other wavelengths are possible, which would allow both imaging of the prostate 18 with embedded seeds 26. The acoustic signals received in the transrectal probe 12 are acquired by the processor 29 in raw form and analyzed therein, as discussed above.
The present invention integrates photoacoustic imaging into existing ultrasonic systems used for interventional treatments, thereby combining the contrast of optical absorption (prostate tissue vs. metallic seeds) with the spatial resolution of ultrasound in deep regions. Because of strong optical scattering, pure optical imaging in biological tissue has shallow imaging depths. In contrast, pure ultrasonic imaging methods can provide high spatial resolution in deeper regions, primarily because ultrasonic scattering is two to three orders of magnitude weaker than those of optical scattering. Also, current ultrasonic probe array technology allows effective focusing of ultrasound beam through transmit/receive beamforming. Ultrasonic imaging, however, detects mechanical properties derived from acoustic impedance mismatch, which sometimes limit ultrasound imaging quality, sensitivity, and/or depth of penetration.
To this end, photoacoustic imaging overcomes the limitations of existing pure optical and pure ultrasonic imaging. As a result, manifold advantages are obtained, including seed tracking, dynamic dosimetry, effective edema/swelling localization, real-time photoacoustic/ultrasonic fusion, cost effective system, and safety.
Although the present invention has been described in connection with preferred embodiments thereof, it will be appreciated by those skilled in the art that additions, deletions, modifications, and substitutions not specifically described may be made without department from the spirit and scope of the invent on as defined in the appended claims.
This application claims the benefit of U.S. Provisional Patent Application No. 61/304,626, filed on Feb. 15, 2010, which is hereby incorporated by reference for all purposes as if fully set forth herein.
Filing Document | Filing Date | Country | Kind | 371c Date |
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PCT/US11/24917 | 2/15/2011 | WO | 00 | 12/27/2012 |
Number | Date | Country | |
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61304626 | Feb 2010 | US |