Patent Application
20190046106
The present invention relates generally to the fields of molecular biology and medicine. More particularly, it concerns imaging and the diagnosis and treatment of cancer with a focus on prostate cancer.
In the United States, prostate cancer (PCa) has been the most commonly diagnosed cancer in males and is consistently among the leading causes of cancer-related deaths of men. According to the “2006 Cancer Facts and Figures” published by the American Cancer Society, an estimated 234,460 new cases of prostate cancer will be diagnosed and 27,350 men will die of prostate cancer in the United States alone in 2006. Most of the deaths from prostate cancer are related to an adjunct disease, in which patients present with bone metastasis and soft-tissue involvement.
The risk of Extraprostatic extension (EPE) and seminal vesicle invasion (SVI) are adverse prognostic factors in prostate cancer in patients with clinically localized disease typically remains at about 10% to 20%, despite definite local therapy. The skeleton is the most common site for metastases in a variety of cancers, among which breast and prostate cancers account for over 80% of cases causing the great morbidity due to intractable bone pain, pathological fractures, hypercalcemia and nerve compression. Once the tumor spreads to bone, it can become unresponsive to standard therapeutic treatments, and there is presently no effective treatment of bone metastases.
Therefore, the present invention describes concepts that hold the potential to provide an almost non-invasive early detection via a ultra-sound rectally inserted detection device which will show prostate cancer (and many other types of cancer) in many stages of its development. The present invention will detect tumors, for example, in a simplified model of tumor cell in which the tumor is a sphere at least as small as 1 mm diameter. Such a system and method can yield resolution for tumor detection with a 5× to 10× in linear dimension and 100× to 1000× smaller tumor volumes than detectable by contrast and implemented at a small fraction of the cost or imaging time of an MRI, or traditional TRUS. With current technology, resolutions of a 5 mm spherical cancer cell approximation are only possible. The present invention deploys techniques to increase the signal to noise ratio, such as signal averaging and a larger aperture, phased array system with image reconstruction.
Additionally, with breakthroughs in fluorophores carrying peptides that bond to nerve cells, thus permitting nerve protection during normal surgery or new methods enabled by the systems and methods described herein. If a surgeon can visualize nerves during prostate cancer elimination (either visual nerve imaging or photo-acoustic nerve imaging overlaid on prostate bed), the system holds the potential to significantly reduce nerve damage and facilitate very high quality care, scalable to many patients at minimal cost. Therefore, it would be beneficial to detect and remove any involved prostrate carcinomas before they can metastasize.
Photo Acoustic Imaging
The photoacoustic effect was first discovered by Alexander Graham Bell. When a molecule absorbs a light particle, if enough molecules absorb enough light, an ultrasound pulse is emitted. That is, after absorption of optical light, the molecules in the medium heat up briefly, expand, and emit sound waves in the megahertz (Mhz) region of the electrical frequency spectrum.
For example, a laser probe may be inserted into the urethra and laser light from the laser probe from inside the urethra can excite a prostate cancer sticky peptide inserted into the subject, such a fluorophores which will then emit sound waves when the laser light is removed, thus permitting the identification and the location of the cancerous region of the prostrate. A peptide is any member of a class of compounds of low molecular weight that yield two or more amino acids on hydrolysis can be compounded to attach to a cancer cell, such as a prostate cancer cell or another cancer cell.
Alternatively, the normal rectal position of prostate ultrasound or trans rectal ultrasound (TRUS) probes when the urethra is too complex and small, and ultrasound probes through rectal access will be easier.
In addition, the tumor can be ablated for example, with a High intensity Focused Ultrasound (HIFU) tumor destruction via the probe. The probe, using beamforming via an array, can yield a focused beam at the tumor. The array permits the beam have varying apertures, so that the beam has very small side lobes, and does not do significant damage to healthy prostate tissue or nerves.
With reference to the Figures, wherein like numerals indicate like parts throughout the several views,
The probe 20 connects to a processor unit 52 (
As the fluorophore changes state, the fluorophore emits a radio frequency energy due to a photoacoustic effect signal due to transient thermoelastic expansion. The radio frequency energy is received by the electronically steerable receiver 32 and returns a second signal to the processor unit 52.
The second signal is analyzed by the processor unit 52, for example, using digital signal processing and/or other algorithms to map the prostate and the prostate cancer. The processor can use at least one of a graphics processing unit (GPU) and one or more computer processors of a computing system to interpolate said transient thermoelastic expansion and produce a voxel representation of the prostate and an area proximate the prostate.
As the fluorophore changes state, the fluorophore emits a radio frequency energy due to transient thermoelastic expansion. The radio frequency energy is received by a photoacoustic sensor 42 and returns a second signal to the processor unit 52.
The second signal is analyzed by the processor unit 52, for example, using digital signal processing and/or other algorithms to map the prostate and the prostate cancer. The processor can use at least one of a graphics processing unit (GPU) and one or more computer processors of a computing system to interpolate said transient thermoelastic expansion and produce a voxel representation of the prostate and an area proximate the prostate.
The photoacoustic probe detection system 10 is deployed after a fluorophore peptide dye conjugate compound which has at least one absorption wavelength in a range of 380 to 1400 nm is injected into the patient, for example, 700 nanometer wherein said compound attaches to a prostate-specific membrane antigen (PSMA) expressed by a prostate cancer cell. A photo-acoustic imaging probe 20, having an operative end configured for scanning a prostrate, said photo-acoustic imaging probe to be inserted in at least one of a rectum, urethra, or placed proximal the prostate.
The photo-acoustic imaging probe 20 has an emitter 30 to emit a first signal towards the prostrate and a prostate cancer cell to excite said fluorophore peptide dye conjugate compound. The probe 20 has a receiver 32 to receive a second signal from said fluorophore peptide dye conjugate compound, thereby indicating a cancerous region of the prostrate. The processor unit 52 connected to said probe 20, wherein said processor unit 52 is configured and operable for receiving and processing said second signal to produce a tomographic representation of said prostrate. The processor unit 52 contains at least a processor, a read memory, a read-write memory, an instruction set and an interface.
In an embodiment, the first signal is produced in processor unit 52 and fiber optically coupled to the photo-acoustic imaging probe 44, wherein said first signal is generated by at least a laser, and a photo diode.
In another embodiment, the first probe 20 or the the photo-acoustic imaging probe 44 comprise at least one of a phased array of ultrasound sensors, a set of monolithic single channel ultrasound sensors, and an ensemble of phased array of ultrasound sensors.
The processor unit 52 can contain at least one of a graphics processing unit (GPU) and one or more computer processors of a computing system to interpolate said transient thermoelastic expansion and produce a voxel representation of the prostate and an area proximate the prostate. The processor unit 52 can also contain a memory unit to store said voxel representation of the prostate and the area proximate the prostate.
The processor unit 52 is communicatively coupled to a screen, a virtual reality display mechanism, and an augmented reality display mechanism to display a visual representation of the prostate and the cancer, for example a 3-D tomographic representation.
The fluorophore peptide dye conjugate can be compounded to attach to a cancerous region in at least one of a breast, a lung, a bronchus, a colorectal region, a uterine corpus, a bladder and a thyroid. Additionally, the fluorophore peptide dye conjugate can be compounded to attach to attach to a cavernous nerve adjacent the prostate, thereby the cavernous nerve to be differentiated from the prostrate and the cancerous region.
Furthermore, a fluorophore peptide dye conjugate can be compounded to attach to a medically important cell in a medically important region of interest in at least one of a heart region, a brain region, a chest region, a stomach region, a leg region, an arm region, and a head region, thereby a detection of nerves is feasible due to a long path length of light, and a low scattering of said second signal. Additionally, a nerve fluorophore peptide dye conjugate can be compounded to attach to attach to a nerve cell in at least one of a breast, a lung, a heart, a bronchus, a colorectal region, a uterine corpus, a bladder, a thyroid and any corpus part.
In another embodiment, the photoacoustic imaging system 10 is configured and operable with high frequency ultrasound (HIFU) cancer ablation system to ablate said cancer region via a feedback loop. For example, until said photoacoustic imaging system 10 determines that a voxel cancer value is less than less than 5 percent of an initial cancer voxel value associated.
In another embodiment, the photoacoustic imaging system 10 obtains measurements of the prostrate with the probe before injecting the fluorophore peptide dye conjugate compound to obtain a first set of baseline data of the prostrate. Then obtaining measurements of the prostrate with the probe after injecting the fluorophore peptide dye conjugate compound to obtain a second set of data of the prostrate. A prostate image is obtained by subtracting the first set of baseline data from the second set, thereby producing a differential image showing only the cancerous tissues.
In another embodiment, the photoacoustic imaging system 10 includes a 3-D coordinate orientation sensor for determining a location and orientation of the probe using.
Peptides for Both Visual and Photoacoustic Nerve Identification
Peptides can carry fluorophores to nerve cells. This means, for example, during a traditional prostatectomy, nerves could be visualized and over laid on the surgical field of view. In an embodiment of the present invention, a different fluorophore be used to give a different spectral output, so nerves and prostate cancer can be differentiated. That is, in use, one could pulse with one color laser to illuminate on nerve fluorophore, record the photoacoustic or visual image, then pulse with a different laser to excite the fluorophore on the PSMA.
Thus an embodiment of the present invention is to have photo-acoustic identification of the nerves as well as the cancer. For example, a fluorophore is excited with near infrared light. An ultrasound detector (not shown) is deployed to receive the signals. An advantage to this embodiment is this allows much greater depth penetration, and allows cancers to be seen and identified that are out of visual field.
The disclosure has been described in an illustrative manner, and it is to be understood that the terminology which has been used is intended to be in the nature of words of description rather than of limitation. Many modifications and variations of the present disclosure are possible in light of the above teachings, and the disclosure may be practiced otherwise than as specifically described.
The subject patent application claims priority to and all the benefits of U.S. Provisional Patent Application No. 62/542,342, which was filed on Aug. 8, 2017, which is herein incorporated by reference in its entirety.
| Number | Date | Country | |
|---|---|---|---|
| 62542342 | Aug 2017 | US |
