Waveform energy influence of objects using feedback control

A control system for delivering energy waveform radiation to influence in vivo tissue is described. For the system, the energy waveform radiation is generated by a radiation unit and is directed along a pathway to the tissue and a registration unit is provided to identify a start place relative to the in vivo tissue. Also, a monitor is provided to compare the start place with a base reference to measure an error signal between the start place and base reference. With this measured error signal, a controller operates the radiation unit using input from the monitor to effectively attain and maintain a zero error signal. More specifically, the controller can provide operational parameter inputs to the radiation unit for configuring the waveform radiation including a radiation frequency, f, and a volume intensity level, v, for the radiation and an exposure time interval, ti.

FIELD OF THE INVENTION

The present invention pertains generally to systems and methods for influencing objects using waveform energy. More particularly, the present invention pertains to systems and methods for influencing cellular structures to morph or transition into a target value or condition, by applying waveform energy to the structures. The present invention is particularly, but not exclusively, useful for influencing objects by applying waveform energy to them while controlling the process using a feedback control system.

BACKGROUND OF THE INVENTION

Feedback can be used to make adjustments to one or more system inputs, to thereby drive a system output toward a target value or condition. In this process, information output by the system is used to determine the appropriate system input adjustments. In some instances, an ability to understand the relationship between output information and one or more input adjustments can allow a process to be developed that achieves results that are otherwise unobtainable using uncontrolled or so-called “open-loop” type systems.

One process in which feedback can be advantageously used involves the exposure of tissue to waveform energy. In this regard, it is known that exposing tissue to waveform energy can cause permanent changes to the tissue. In particular, it has been recognized that sonic waves and other electromagnetic waves can be employed to cause transformative or morphological changes in cellular structure. Not surprisingly, many of these changes may be very beneficial. Thus, within the medical community there is increasing interest insofar as the extent to which such changes may be employed to beneficially alter the functionality of a cellular structure.

From a mechanical perspective, each individual cellular structure (tissue cell) has a natural frequency at which it will oscillate (i.e. vibrate) when subjected to an external force. Another consequence of this natural frequency is that cellular structures will respond to periodically applied external forces having certain frequencies, such as the natural frequency, quite differently than they will respond to external forces having other applied frequencies.

From a biological perspective, each cell type (e.g. a liver cell) will have observable characteristics which naturally result from the cell's environment. A set of these observable characteristics is generally referred to as a phenotype. Further, it is known that the set of characteristics for a defined phenotype of a cellular structure can be epigenetically influenced by externally applied forces. Moreover, this can happen regardless of whether the cellular structure is influenced in vivo or in vitro.

In light of the above, it is an object of the present invention to provide efficient systems and methods for influencing cellular structures when waveform energy is applied to the structures. It is another object of the present invention to provide a system and method for directing waveform energy to an object which utilizes closed-loop feedback control to obtain an improved interaction between the waveform energy and the object. It is yet another object of the present invention to apply waveform energy to tissue under feedback control to epigenetically influence tissue cells, and to thereby alter the functionality of an in vivo, or an in vitro, target tissue. Yet another object of the present invention is to provide a system and method for waveform energy influence of objects using feedback control which is easy to use and commercially cost effective.

SUMMARY OF THE INVENTION

In accordance with the present invention, a control system for delivering energy waveform radiation to influence in vivo tissue includes a radiation unit. In particular, the energy waveform radiation that is generated by the radiation unit is directed along a beam pathway toward the tissue. For the present invention, a registration unit is provided to identify a start place relative to the in vivo tissue, to establish where the radiation is to be directed.

A monitor is provided for the control system to compare the start place vis-a′-vis a base reference. This is done by measuring an error signal between the start place and the base reference. With this error signal measured by the monitor, a controller in the system operates the radiation unit to effectively attain and maintain a zero error signal. More specifically, the controller can adjust the beam pathway and/or provide operational parameter inputs to the radiation unit for configuring the waveform radiation. For example, these operational parameter inputs can include a radiation frequency, f, a volume intensity level for the radiation, v, and an exposure time interval, t1. When pulsed radiation is employed, an additional operational parameter can be input to the radiation unit, namely, the pulse duration, td, can be specified by the controller. In some implementations, a computer is used for coordinating respective operations of the radiation unit, the monitor, and the controller.

In a first embodiment of the present invention, the control system includes an imaging unit for creating an image of the in vivo tissue to be radiated. For example, the imaging unit can be an Optical Coherence Tomography (OCT) imaging unit, a Magnetic Resonance Imaging (MRI) imaging unit, a Positron Emission Tomography (PET) imaging unit or a Computerized Axial Tomography (CAT) imaging unit. For this embodiment, the registration unit identifies a start place relative to the in vivo tissue in the image. For instance, the start place can be a point where a focused beam of the energy waveform radiation intercepts the in vivo tissue. In the event, the monitor is connected with the imaging unit to compare the start place with the base reference, such as a target point identified on the image of the in vivo tissue. The distance between the start place and base reference is then measured and used as an error signal to control the operational parameters of the radiation unit. In one implementation, the target point is periodically repositioned on the image of the in vivo tissue. In some cases, the target tissue is moved in a pattern relative to the in vivo tissue in accordance with a selected protocol.

In another embodiment of the present invention, the base reference is a predefined phenotype for the in vivo tissue, and the start place is a cellular structure of the in vivo tissue. For this embodiment, the monitor can be an appropriate sensor for obtaining a set of observable characteristics of the tissue to determine the required phenotype. Alternatively, this monitoring function can be performed by the periodic performance of a biopsy. In the event, management and control of the protocol by the computer is terminated when the phenotypic response corresponds with the desired phenotype.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

In accordance with the present invention, a control system10for delivering an energy waveform radiation11to influence in vivo tissue12includes a radiation unit14. As shown, the energy waveform radiation11is generated by the radiation unit14and is directed along a pathway16to the tissue12.FIG. 1also shows that the radiation unit14will be positioned at a distance, d, from the target tissue12. Typically, the distance d will be greater than about 10 millimeters (d>10 mm).

For the system10shown inFIG. 1, the energy waveform radiation11may be focused or unfocused and may be pulsed or continuous. The radiation11can be directed onto exposed tissue12to influence the exposed tissue12, or the radiation11can be directed to pass through surface tissue to a subsurface location for the purpose of influencing tissue12located below the surface. As contemplated for the present invention, both soft tissues and hard tissues may be influenced using the systems and methods described herein.

As envisioned for the present invention, the radiation11to be employed for influencing target tissue12may be of any waveform energy known in the art. It may be radiation in the electromagnetic spectrum. For many instances, however, the radiation will be between wavelengths of 10−25m to 103m. It may also be periodic mechanical vibrations. In this latter case, the radiation11may be acoustic sound waves in the range between 20 Hz and 20 kHz, and may also include infrasound waves (<20 Hz) and ultrasound waves (>20 kHz). Further, the tone of the radiation11may be either pure (single frequency) or complex (multi-frequency).

FIG. 1shows that the radiation unit14receives operational parameters18as an input. These operational parameters18can include a radiation frequency, f, a volume intensity level for the radiation, v, and an exposure time interval, ti. When pulsed radiation11is employed, an additional operational parameter18can be input to the radiation unit14, namely, the pulse duration, td, can be specified by the controller28.

Continuing now with reference toFIG. 1, it can be seen for the present invention that a registration unit20is provided which receives an image of the tissue12that is generated by an imaging unit22. One purpose here is to identify a start place30relative to the in vivo tissue12(seeFIG. 2). The registration unit20then outputs the start place30to a monitor24. In this operation, the imaging unit22can be an Optical Coherence Tomography (OCT) imaging unit, a Magnetic Resonance Imaging (MRI) imaging unit, a Positron Emission Tomography (PET) imaging unit or a Computerized Axial Tomography (CAT) imaging unit.

During an operation of the system10, it is to be appreciated that the energy waveform radiation11which is generated by the radiation unit14will be controlled by a computer34. As envisioned for the present invention, this control will be accomplished using closed-loop feedback control techniques. In overview,FIG. 2depicts the functional aspects of a control circuit19for such an operation.

With reference toFIG. 2it will be seen that several different considerations contribute to the identification of an appropriate input25for the circuit19and its closed-loop control of the system10. As indicated inFIG. 2, a selected combination of these considerations will determine values for the operational parameters18(f, v, and ti) that are necessary for the radiation unit14to generate an effective energy waveform radiation11. Depending on the particular protocol40that is to be followed, the input25will also include the determination of a start place30and a base reference26. Further, a sensor31needs to be employed to provide the necessary feedback information for closed-loop feedback control. The particular type of sensor31that is required will essentially depend on the operational requirements of the protocol40that is to be followed. In turn, all of this depends on the objective(s) to be gained by an operation of the system10.

For one embodiment of the present invention, the objective(s) of protocol40may be to improve the vitality, or alter the functionality of the target tissue12. This will likely include a proper identification, and an accurate location, of the target tissue12for treatment. In this case, the input25will necessarily include information regarding the start place30(e.g. location), to where the waveform energy radiation11is to be directed. It may also need to include a base reference26for accurately and appropriately maintaining the start place30′ (seeFIG. 3A). For this purpose, the sensor31will most likely be an imaging unit22of a type as disclosed above.

For another embodiment of the present invention, the objective of protocol40may be to morph an undifferentiated target tissue12(e.g. target tissue12ainFIG. 3B) into a desired phenotype33(e.g. target tissue12din

FIG. 3B). More specifically,FIG. 3Bshows a sequence of morphed target tissues12during such a transformation (Note: the target tissues12a,12b,12c, and12dshown here are only exemplary). Moreover, for this example, as part of this sequence radiation11ais influencing target tissue12a. Similarly, radiation11cis shown influencing target tissue12c. In a procedure such as this, the input25will necessarily include information of the desired phenotype33(i.e. target tissue12d) that is to be created during the procedure. To do this, an accurate description of the desired phenotype33is necessarily used as the base reference26. As envisioned for this embodiment of the present invention, the sensor31may well be a sequence of biopsy procedures which are periodically performed to titrate the target tissue12.

In accordance with a protocol40for either of the above embodiments, closed-loop feedback control is provided by first establishing the necessary input25for an operation of the radiation unit14. Specifically, this input25(e.g. f, v, ti, start place30and base reference26) is provided to the computer34for controlling and operating the radiation unit14. It is in accordance with the input25that the radiation unit14is activated to generate the waveform energy radiation11. During the protocol40, sensor31records the influence of this radiation11on the target tissue12. Then, based on the progress of this influence, a feedback signal27is generated which is forwarded to the summing point32. At the summing point32, the feedback signal27is added to the input25to thereby generate an error signal that will appropriately adjust the operation of radiation unit14to maintain its operational efficacy.

In further detail, and by referring back toFIG. 1, it can be seen that the controller28of computer34receives an operational protocol40together with other operational information from the monitor24. With these inputs, the controller28operates the radiation unit14. More specifically, the controller28can adjust the beam pathway16and/or modify the operational parameter inputs18to the radiation unit14for configuring the waveform radiation11. Suitable protocols for influencing tissue to obtain a selected tissue response can be found in co-pending, co-owned U.S. patent application Ser. No. 14/488,101, filed Sep. 16, 2014 and titled “System and Method for Sonic Radiation for Influencing Cellular Structures,” the entire contents of which are hereby incorporated by reference herein.

As implied above with reference toFIG. 3A, an embodiment of the present invention which requires directional control over the waveform energy radiation11will preferably include a parabolic speaker42which is affixed to the radiation unit14′. Specifically, speaker42can be employed to project a focused beam of the radiation11in the form of acoustic sound waves to the tissue12′. As shown inFIG. 3A, the radiation11is directed to a focal spot at the start place30′ in the tissue12′. The monitor24(seeFIG. 1) compares information regarding the start place30′ (focal spot), as received from the imaging unit22, with the base reference26′ (i.e. a target point identified on the image of the in vivo tissue). The distance, D, shown inFIG. 3Abetween the start place30′ and base reference26′ is then measured as an error signal and used by the controller28to adjust the radiation unit14′, and for directional control of the radiation11. In one implementation, the base reference26′ (i.e. target point) is periodically repositioned on the image of the in vivo tissue12′. In some cases, the base reference26′ (i.e. target tissue) is moved in a pattern relative to the in vivo tissue12′ in accordance with a selected protocol (e.g. protocol40shown inFIG. 1).

FIG. 4illustrates a procedure44for influencing in vivo tissue12using feedback control. As shown, the procedure44begins by identifying a base reference26(block46) for the in vivo tissue. For the present methods, this base reference26is either a start place30on the target tissue12or a predefined phenotype33for the in vivo tissue. For example, the objective of the procedure44may be the creation of a particular type of stem cell (e.g. liver cell depicted as target tissue12dinFIG. 3B) from an otherwise undefined or undifferentiated cell (e.g. target tissue12ainFIG. 3B). In this case, the desired phenotype33(outcome) will be defined to have the requisite characteristics of the particular type stem cell that is desired (e.g. liver cell). As another example, the objective of a protocol40may be to terminate the viability of a cellular structure, such as by killing cancer cells. Still another example may be to assert directional control over the radiation unit14′ (seeFIG. 3A).

With the base reference26identified, the next step is to adjust the operational parameters18(box48) for the radiation unit14,14′ (seeFIGS. 1, 3A and 3B). As indicated above, the operational parameters18can include, but are not necessarily limited to, the radiation frequency, f, volume intensity level, v, for the radiation exposure time interval, ti, and when pulsed radiation is employed, the pulse duration, td. Once the operational parameters18have been initialized, the next step is to generate the energy waveform radiation11(box50) and direct it toward the targeted tissue12(box52). After an initial exposure of the in vivo target tissue12to the radiation11, the next step is to identify a start place relative to the in vivo tissue12(box54). For example, this can be performed by imaging the tissue12in situ, by using a sensor31(e.g. imaging unit22), or by performing a biopsy on a portion of the tissue12. Next, box56indicates that the start place30is compared with a base reference26to measure an error signal therebetween. If the error signal equals zero (i.e. if the predefined phenotype33has been achieved) (box58) then the procedure is complete (box60). Otherwise, as indicated by arrow62, boxes48,50,52,54and56are repeated. This process is repeated until the error signal is zero (box58) and the predefined phenotype33has been achieved.

While the particular embodiments and implementation of Waveform Energy Influence of Objects Using Feedback Control as herein shown and disclosed in detail is fully capable of obtaining the objects and providing the advantages herein before stated, it is to be understood that it is merely illustrative of the presently preferred embodiments of the invention and that no limitations are intended to the details of construction or design herein shown other than as described in the appended claims.