For optimal phototherapy, there needs to be sufficient light and drug dose present in the target cells for complete cell killing along with sufficient oxygen. Light dose distribution is affected by the local optical parameters (i.e. absorption and scattering) at a therapeutic wavelength, and tissue oxygenation is affected by the vascular parameters such as blood oxygen saturation. Thus, it is desirable to quantify these parameters for accurate light dosimetry and phototherapy monitoring.
During phototherapy treatment field planning, micronodules may not be clinically evident. Drugs (e.g., porphyrins used as photosensitizers in photodynamic therapy or doxorubicin used in chemotherapy) fluoresce strongly and fluorescence signal can provide improved tumor demarcation for accurate light illumination. This allows optimal targeting of tumor cells while preserving the surrounding normal tissue. Thus, an instrument that can provide high contrast for improved tumor demarcation is desired. Raw fluorescence signals, however, are distorted due to strong tissue absorption and scattering, hiding the true fluorescence contrast. Thus, an attenuation corrected quantitative fluorescence imaging system is needed.
Since there is great heterogeneity in optical parameters and drug accumulation as well as tumor size and shape in patients, the light dose needs to be individualized by an instrument that can deliver adaptive light beam shape and intensity on a patient by patient basis.
The following presents a simplified summary in order to provide a basic understanding of some aspects of the innovation. This summary is not an extensive overview of the innovation. It is not intended to identify key/critical elements or to delineate the scope of the innovation. Its sole purpose is to present some concepts of the innovation in a simplified form as a prelude to the more detailed description that is presented later.
In one aspect of the innovation, an endoscopic imaging system is disclosed that includes an endoscope having a first channel and a second channel, a high-power, multi-wavelength light emitting diode (LED) array, a digital micro-mirror device that receives light directed from the high-power, multi-wavelength LED array and generates spatial frequency patterns, and dichroic mirror that separates collected reflectance and fluorescence images.
In another aspect of the innovation, a method of phototherapy is disclosed that includes inserting an endoscope into an internal cavity, projecting spatial frequency patterns through a first channel of the endoscope onto tissue, collecting reflected light through a second channel of the endoscope, relaying the reflected light to a pair of cameras, measuring reflectance in one camera and fluorescence in the other camera, analyzing the reflectance and fluorescence images, extracting absorption and scattering properties of the tissue, and adjusting treatment light intensity and shape based on the absorption and scattering properties.
To accomplish the foregoing and related ends, certain illustrative aspects of the innovation are described herein in connection with the following description and the annexed drawings. These aspects are indicative, however, of but a few of the various ways in which the principles of the innovation can be employed and the subject innovation is intended to include all such aspects and their equivalents. Other advantages and novel features of the innovation will become apparent from the following detailed description of the innovation when considered in conjunction with the drawings.
The innovation is now described with reference to the drawings, wherein like reference numerals are used to refer to like elements throughout. In the following description, for purposes of explanation, numerous specific details are set forth in order to provide a thorough understanding of the subject innovation. It may be evident, however, that the innovation can be practiced without these specific details. In other instances, well-known structures and devices are shown in block diagram form in order to facilitate describing the innovation.
While specific characteristics are described herein (e.g., thickness, orientation, configuration, etc.), it is to be understood that the features, functions and benefits of the innovation can employ characteristics that vary from those described herein. These alternatives are to be included within the scope of the innovation and claims appended hereto.
While, for purposes of simplicity of explanation, the one or more methodologies shown herein, e.g., in the form of a flow chart, are shown and described as a series of acts, it is to be understood and appreciated that the subject innovation is not limited by the order of acts, as some acts may, in accordance with the innovation, occur in a different order and/or concurrently with other acts from that shown and described herein. For example, those skilled in the art will understand and appreciate that a methodology could alternatively be represented as a series of interrelated states or events, such as in a state diagram. Moreover, not all illustrated acts may be required to implement a methodology in accordance with the innovation.
A unique endoscopic platform for disease demarcation, treatment planning, optimized light delivery and therapy response monitoring is disclosed herein. The platform is based on an endoscopic imaging system that allows both quantitative imaging and adaptive beam-shaping for light-based therapy of diseases. The innovation demarcates and treats diseases, thereby improving survival rates of patients.
This single platform quantifies spatial maps of optical parameters and drug fluorescence concentration for treatment planning and light dose optimization as well as tissue oxygen saturation, hemoglobin concentration and blood flow distributions for monitoring light-based therapies. Currently most clinical endoscopes use white light illumination and reflected light visualization by eye or by charge-coupled device (CCD) camera for visual guidance. In addition some clinical endoscopes are used for direct fluorescence signal intensity imaging. The endoscopic system disclosed herein has three main functions: 1) imaging with enhanced contrast, 2) therapeutic light delivery, 3) monitoring the therapy response for predicting or optimizing the outcome with a feedback loop/response. The imaging part involves both quantitative reflectance and fluorescence imaging. Quantitative refers to extracting the actual chromophore and fluorophore concentrations rather than raw intensity counts.
Standard light dosimetry is based on the prescribed incident dose, which does not take into account reflected and scattered light in the lesion. For optimal light dosimetry with complete cell killing and minimal damage to normal tissue, an appropriate treatment field has to be outlined and sufficient dose delivered. The innovative endoscopic system can perform reflectance and fluorescence measurements by using a single light source and two CCD cameras working in parallel for fast data acquisition during phototherapy without treatment light interruptions. Reflectance measurements can quantify tissue absorption and scattering, which are crucial for accurate light dosimetry in tissue. Reflectance measurements also allow quantification of tissue blood oxygenation and blood volume which are useful for assessing the therapeutic response. The endoscopic system can also assess absolute drug concentration for improved contrast during treatment field planning, and drug dose (concentration) for accurate light dosimetry, and can quantify phototherapy induced physiologic changes (e.g. changes in oxygenation) more accurately and thus inform about the therapy response. Drug (e.g., photosensitizers for photodynamic therapy or doxorubicin used in chemotherapy) fluorescence measurements allow quantification of fluorescence concentration. The endoscopic system determines the optimal light dose according to light attenuation and drug concentration distribution on an individual basis. The endoscopic system allows for real-time treatment light adjustment in the same platform for tumors of any size and shape by adjusting light intensity according to drug concentration so that optimized light delivery can be increased for the cases of cells that have low amount of drug concentrations.
The endoscopic system combines guidance of phototherapy treatment field, the optimization of the treatment light and therapy monitoring in the same platform. The endoscopic system introduces a single platform that allows both imaging and treatment light delivery according to any tumor size and shape that is locally identified by the spatial distribution of drug fluorescence concentration rather than the prescribed fixed dose and shape. The endoscopic system allows near real-time dose optimization on an individual basis by quantifying the spatial distribution of drug concentration and adapting the treatment light dose accordingly. The endoscopic system can be applied to phototherapy optimization of many sites of internal cavities including lung, oral, ovarian, esophagus and colon as well as more accessible sites such as skin, brain and breast.
The endoscopic system provides a method of delivering light using feedback control, wherein dose metrics (drug concentration, tissue blood flow and oxygenation) are monitored and the delivery of treatment light is adjusted accordingly to optimize treatment response.
The endoscopic system allows light delivery concurrently during reflectance and fluorescence measurements. Reflectance measurements provide optical properties (absorption and scattering) of tissue, which in turn allows a) light intensity distribution throughout tissue volume, which is related to light dosimetry in tissue, and b) tissue blood oxygen saturation and blood volume, which is related to treatment response. Fluorescence measurements allow quantification of drug concentration during therapy, which can lead to optimal drug light and drug delivery to target areas.
Referring now to the drawings,
The endoscopic system 100 includes a high-power, multi-wavelength LED array with bandpass filters at the desired wavelength. The light is directed onto a digital micro-mirror device (DMD), which generates the appropriate spatial frequency pattern. Reflectance and fluorescence images are separated by a dichroic mirror. The endoscopic system 100 can provide high contrast for improved disease demarcation and perform light-based therapies. Light delivery can be adapted according to the sizes and shapes of disease that will be locally identified by the spatial distribution of drug concentration.
More specifically, digital micro-mirror device (DMD) projects spatially modulated light (structured illumination) onto tissue and the measured spatially modulated tissue response function contains information of optical absorption, scattering and fluorescence. Multiple frequencies of a sine wave pattern are generated at three phases (0°, 120° and 240°). The frequencies vary from low (
Referring to
Most clinical endoscopes are utilized for visualization during screening without any quantitative imaging capabilities. Several fluorescence endoscopes have been developed to date but they mainly measure the relative fluorescence intensity not the concentration of the fluorescence drug. These approaches are semi-quantitative; obtained results can vary and depending on the operator, methods, and instrument themselves.
The innovative endoscopic system 100 disclosed herein is based on quantitative reflectance and fluorescence imaging. This device is capable of three main functions: 1) reflectance-related quantitative measures, such as optical absorption and scattering, tissue oxygen saturation and blood flow, and 2) quantitative fluorescence measures such as drug concentration, 3) provide adaptive light treatment illumination scheme. The first two are related to imaging (diagnostic), and the third is related to therapy. Thus, the device is called theranostic light endoscope.
One advantage of the endoscopic system 100 is that the same DMD chip is used for imaging (quantification of optical parameters and drug concentration) as well as light treatment. This allows each pixel from the images to correspond one-to-one with the treatment light. With this setup, fluence rate can be controlled pixel by pixel allowing for precise beam-shaping and fluence rate control.
The endoscopic system 100 provides fluorescence concentration measurements during therapy without requiring interruption, thereby providing quantitative feedback for adaptive light illumination, which is expected to lead to improved treatment outcome. The endoscopic system 100 provides reflectance measurements during therapy without requiring interruption, allowing more accurate assessment of the kinetics of therapy related parameters (such as tissue blood oxygenation) that are indicative of the treatment response.
Referring to
In another potential embodiment an endoscopy device, such as is described above, may be applied to neuroscience rather than cancer. Such an endoscope could image neuronal cells (imaging) and then trigger the cells with laser light (neuromodulation). The triggering mechanism for this particular embodiment is based on laser-induced heat that creates changes in action potentials resulting in cell triggering.
Unique characteristic of the endoscopic system is that it can provide feedback for treatment light adjustment by using drug concentration distribution, rather than delivering a fixed light intensity. This provides optimal light dose for complete cell kill or optimal drug delivery for improved therapy outcome. As mentioned and as shown in
The innovative endoscopic system allows quantitative fluorescence imagining in addition, to white-light visualization. The system can quantify fluorescence concentration. In addition, the system can quantify optical parameters of absorption and scattering and oxy deoxy-hemoglobin concentrations, thus tissue blood oxygen saturation and blood volume.
The system can be used in imaging and treating of micrometastasis in intraperitoneal cavity, imaging the brain during surgery for surgical guidance or any drug based intervention as well as in oral, lung, esophageal, cervix cancer detection and treatment. Diagnosis and treatment of gastrointestinal tract, pancreas, urinary bladder, breast. Diagnosis of vulnerable and non-vulnerable atherosclerotic plaques, Alzheimer Disease.
What has been described above includes examples of the innovation. It is, of course, not possible to describe every conceivable combination of components or methodologies for purposes of describing the subject innovation, but one of ordinary skill in the art may recognize that many further combinations and permutations of the innovation are possible. Accordingly, the innovation is intended to embrace all such alterations, modifications and variations that fall within the spirit and scope of the appended claims. Furthermore, to the extent that the term “includes” is used in either the detailed description or the claims, such term is intended to be inclusive in a manner similar to the term “comprising” as “comprising” is interpreted when employed as a transitional word in a claim.
The above embodiments have been described with brevity (e.g., in terms of modules) in light of what is well known in the art. However, it should be understood that some of the inventive functionality, features and benefits recited herein may be carried out in connection with the use of computers, processors, software, computer logic, hardware and other implements known to one of ordinary skill in the art as necessary.
This application claims the benefit of U.S. Provisional Patent application Ser. No. 62/291,261 entitled “LIGHT ENDOSCOPE SYSTEM FOR IMAGING, LIGHT DELIVERY, AND THERAPY RESPONSE MONITORING” and filed Feb. 4, 2016. The entirety of the above-noted application is incorporated by reference herein.
Number | Date | Country | |
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62291261 | Feb 2016 | US |