Abstract:
A system and method for in-vivo monitoring for changes in body proteins over time includes an intelligent, implantable image capture system. An embedded processor controls activation of lighting for imaging proteins in surrounding tissue. A base image is captured and resulting data used in comparison with image data from one or more subsequent image captures to indicate progression of tissue changes, such as may occur with diseased tissue.

Description:
TECHNICAL AREA 
       [0001]    This application relates generally to a method and apparatus for clinical diagnosis. The application relates more specifically to an implantable sensor for detection and repair of progressive physiological conditions. 
       BACKGROUND 
       [0002]    Systems and methods of observing physical maladies continue to evolve rapidly. Earliest observations as to a patient&#39;s physical condition involved visual inspection by a clinician. Systems evolved to include analysis by surgical exploration and by testing physical properties of a subject or a subject&#39;s tissue. More recently, clinicians use devices such as X-ray, computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) and near-infrared spectroscopy (NIRS) for medical diagnostics. 
         [0003]    Tools such as those noted above are useful to facilitate patient diagnostics and to provide a clinician with information about a patient&#39;s current physical condition. 
       SUMMARY 
       [0004]    In accordance with an example embodiment of the subject application, an implantable diagnostic system includes a power supply and an electromagnetic wave generator configured to generate an electromagnetic wave to biological tissue. An image sensor captures an image from the electromagnetic wave generator after exposure of the biological tissue. An analog front end circuit generates image data from a captured image. The electromagnetic wave generator is configured to be selectively enabled by the processor. The processor completes a plurality of image capture operations and stores image data in the memory for image captures. The processor then compares image data from an earlier image capture to a subsequent image capture and generates comparison data which is then output. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0005]    Various embodiments will become better understood with regard to the following description, appended claims and accompanying drawings wherein: 
           [0006]      FIG. 1  is an example embodiment of a medical diagnostic or monitoring or repair system; 
           [0007]      FIG. 2  is an example embodiment of a biosensor; 
           [0008]      FIG. 3  is an example embodiment of an imaging system; 
           [0009]      FIG. 4  is an example embodiment of a CMOS image capture system; 
           [0010]      FIG. 5  is an example embodiment of a filter; 
           [0011]      FIG. 6  is a flowchart of example operations of a biosensor; and 
           [0012]      FIGS. 7-9  are charts that graphically illustrate example characteristics of biosensor imaging. 
       
    
    
     DETAILED DESCRIPTION 
       [0013]    The systems and methods disclosed herein are described in detail by way of examples and with reference to the figures. It will be appreciated that modifications to disclosed and described examples, arrangements, configurations, components, elements, apparatuses, devices methods, systems, etc. can suitably be made and may be desired for a specific application. In this disclosure, any identification of specific techniques, arrangements, etc. are either related to a specific example presented or are merely a general description of such a technique, arrangement, etc. Identifications of specific details or examples are not intended to be, and should not be, construed as mandatory or limiting unless specifically designated as such. 
         [0014]    In accordance with example embodiments of the subject application, a system and method for improved analysis of human tissue facilitates detection and monitoring of a patient&#39;s current physical condition that may degrade or otherwise vary over time. Progress of a condition may be unique to a particular patient. Analysis may also target a particular condition by modifying aspects of the system to target it. 
         [0015]      FIG. 1  illustrates an example embodiment of a medical diagnostic or monitoring system  100 . In the illustrated example, various sulcus regions, depressions and grooves in the brain, are shown in a human brain  110 . It will be appreciated that the brain is used for illustration of an example embodiment and that the biosensor  200  can suitably be applied to, implanted or embedded with any suitably tissue facilitating in-vivo monitoring of patients or subjects. In brain physiology, one or more protein islands  120  can signify an accumulation of proteins such as beta amolyd or Tau proteins. Such protein islands  120  may also contain a marker, such as oxytocin. In the illustrated example, biosensor  200  is placed on brain surface tissue, and may suitably be disposed so as to contact protein island  120 . Oxytocin is detected in connection with the example embodiment herein, but it will be understood that any suitable marker can be used. 
         [0016]    Turning now to  FIG. 2 , illustrated is an example embodiment of biosensor  200  that suitably includes CPU  204 , memory  208  and power unit  214 . Power unit  214  is suitably comprised of any suitable power source, such as a battery. It will be appreciated that power can also be supplied by a generator operable from ambient heat or via wireless power transmission. Biosensor  200  includes an imaging system  218 , comprised of an imaging array  222  suitably formed from a solid state image capture array such as a charge-coupled device (CCD) array, suitably including a lensing system as will be understood by one of ordinary skill in the art. Imaging array  222  works in concert with an analog front-end (AFE)  226 . AFE  226  is comprised of analog signal conditioning circuitry that suitably uses operational amplifiers and filters to provide a configurable and flexible processing module, and which functions to interface with sensors and perform analog to digital conversion. In the illustrated example, AFE  226  interfaces with imaging array  222  to perform digital image capture. By way of further example, AFEs include Texas Instruments products ADS  1298 , AFE  440  and AFE  460 . 
         [0017]    By way of further example. AFE  226  suitably includes a detection circuit sensitive to flux intensity signals that are associated with monitoring or detection of specific tissue conditions as will be detailed further below. In a particular example embodiment, the AFE  226  includes a programmable amplifier having a set effective number of bits (ENOB) for analog to digital (A/D) conversion, such as a 20 bit resolution and high dynamic range above 100 dB. When working in concert with imaging array  222 , for example as would be implemented in a CCD camera, the AFE  226  suitably shares a set of columns with the imaging array  222 . Implementation of AFE  226  facilitates detection of low level fluorescence to facilitate monitoring and detection as illustrated further below. 
         [0018]    Imaging system  218  suitably includes a filtering system for selecting one or more electromagnetic wave frequencies for attenuation or enhancement to enhance specific detection operations specific to a particular condition. Suitable imaging filtering systems will be detailed further below. Imaging system  218  interfaces with a video output  230  to facilitate image capture and processing, suitably controlled or tuned, with field programmable gate array  234  (FPGA), such as XCV8 series FPGAs. Tuning of image capture, suitably coupled with filtering of electromagnetic input, such as light, allows for capturing of diagnostic images for specific conditions as will be detailed further below. A transmitter or receiver unit  238  facilitates data communication, such as via a wireless data communication via antenna  242 . In a configuration, wireless power transmission can be accomplished via application of oscillating magnetic waves to antenna  242 . 
         [0019]    The example embodiment of  FIG. 2  facilitates capture of a series of images. An initial or earlier captured image has a corresponding value suitably stored in memory  208  as a baseline value. Image values from subsequently captured images are compared, and physiological changes detected as a result of such comparison. Detection of changes over time, particularly in connection with a malady to which the system is filtered and tuned, allows for diagnostics over time to detect maladies that may not otherwise be detected at all. 
         [0020]      FIG. 2  also illustrates a light generation system suitably comprised of an electromagnetic wave illumination system, illustrated as light-emitting diode (LED) array  240  suitably powered by power unit  214 . LED array  240  is enabled under control of one more processors, such as CPU  204 , as is imaging system  218 . Thus, control of lighting and image capture is choreographed by the CPU  204  so as to provide for capture of a series of images over a duration, such as a preset interval, while minimizing power drain. 
         [0021]    Biosensor  200  suitably includes one or more electrodes  250 , illustrated as electrodes  250   a ,  250   b ,  250   c  and  250   d . Electrodes  250  are suitably powered by analog power source  260 , which is suitably formed by inverting DC voltage which may be presented by power unit  214 . Analog power source  260  is suitably under CPU control, such as CPU  204 , or by a dedicated CPU controller  270 . Electrodes  250  facilitate tissue stimulation for further diagnostics or treatment of tissue maladies. By way of further example, the electrodes  250  suitably provide open or closed loop control and delivery of electrical impulses. This may be done pre-imaging, during imaging, or post-imaging, depending on the particular application and target protein or proteins. As will be detailed further below, biosensor  200  suitably acts in conjunction with a filter, such as a light filter. Tuning for imaging one or more particular proteins is suitably accomplished by a combination of filtering and tuning. Filter characteristics input to the CPU  204  for processing, combined with protein characteristics, facilitate tuning the imaging array  222 , such as by block, row, column or pixel level. Tuning suitably includes adjustment of illumination, such as via control of LED array  240 . Available control options include selective illumination of individual or groups of LEDs. The LED array  240  is further suitably comprised of LED elements having different spectral outputs. Thus, selective enablement of elements or element intensity allows for engineered illumination to target specific proteins. As noted above, this is particularly advantageous when coupled with filter properties engineered for detection of one or more target proteins. 
         [0022]    Referring now to  FIG. 3 , illustrated is an example embodiment of an imaging system  300 . An image capture system  310  includes an image sensor  314 , suitably coupled with scan circuit  318 , A/D converter  322  and buffer  326 . The image capture system  310  can include an array such as imaging array  222  of  FIG. 2 . Captured digital images are communicated to image processing system  340  for further processing by image signal processor  344 , suitably in concert with one or more buffers such as buffers  350   a ,  350   b  and  350   c.    
         [0023]      FIG. 4  illustrates an example embodiment of a CMOS image capture system  400 . As will be appreciated by one of ordinary skill in the art, the example CMOS image capture system  400  includes CCD array  404 , suitably comprised of sensor elements for complementary primary color image capture, such as capturing of red, green and blue spectral components. This is suitably accomplished by capturing pixels for the primary colors with neighboring CCD elements, such as red element  410 , green element  412  and blue element  414 . Captured images are suitably compiled within frame assembler  420  and communicated via output controller  424 . Image capture system  400  suitably includes secondary support circuitry as illustrated and as will be understood by one of ordinary skill in the art. 
         [0024]      FIG. 5  illustrates an example embodiment of a filter  500 , suitably disposed in conjunction with light communicated to an image capture array and lensing system, such as a CCD camera. Filtering via a light transmissive medium facilitates removal of one or more frequencies that may be unrelated to a particular condition and the presence of which would hinder capture of light of interest to a particular condition. Similarly, filter properties are suitably altered to accentuate frequencies that may be particularly associated with a particular condition. By way of particular example, oxytocin is associated with many physical conditions, including autism. Beta amolyd protein may be associated with dementia, Huntington disease or other disorders, and TAU protein may be associated with Alzheimer&#39;s disease. Oxytocin is associated with a yellow signal correlation centered around a wavelength of approximately 405 nm. Accordingly, detection of autism can be suitably accomplished by filtration and tuning for light in the yellow spectrum. Further refinement is suitably accomplished by addition of dyes or other substances that facilitate further refinement. 
         [0025]    Analysis of captured images allows for medical diagnoses, but is also suitably used in connection with dosing or electrical stimulation for treatment. In connection with monitoring of brain activities, brains are associated with biological waste management processes that degrade over time, which degradation is detectable by the subject system. The subject system suitably includes closed-loop control to compensate for such degradation. 
         [0026]    While filter  500  is suitably comprised of any electromagnetic wave transmissive medium, properties which allow one or more selected wavelengths, or wavelength ranges, are advantageously used in conjunction with imaging different protein characteristics. In the example embodiment of  FIG. 5 , filter  500  is comprise of a substrate  510  onto which is deposited one or more layers, illustrated as layer  520  and layer  530 . In another embodiment, the filter is pseudomorphic for engineered filtering characteristics. Layer properties, as well as thicknesses, are suitably configured in accordance with a particular application for one or more target proteins. Engineered filters, such as pseudomorphic filters that use pseudomorphic crystals, are suitably comprised of one or more layers formed by spin-on-glass deposition on a substrate. The substrate may be comprised of a semiconductor, such as a CMOS wafer and may comprise deposition on a CCD array. Such deposition may also comprise lensing relative to camera pixel capture elements. In the example embodiment of  FIG. 5 , electromagnetic radiation, such as multi-spectra light  540  is reflected from or passed through a protein of interest. Layer  530  is engineered for light transmission and amplification, at least in a particular optical band, such as yellow. Light amplification may be accomplished by doping constituents, and energy for amplification in a certain band may come from energy in other bands. Layer  520  is engineered to filter light from wavelengths other than that desired. For example, layer  520  can filter infrared light. Thus, the light is communicated through translucent or transparent layer  510  before being communicated to a light sensor, such as a CCD pixel. 
         [0027]    Turning now to  FIG. 6 , illustrated is an example embodiment of a flowchart  600  suitably implemented in code running on one or more processors of biosensor  200 . The process suitably commences at block  602  and proceeds to block  606  where a determination is made as to whether the biosensor is ready for imaging or whether it is to be preset. For presetting, progression is made to block  610  and data is retrieved relative to characteristics of one or more proteins of interest. Next, CCD characteristic data is retrieved at block  614  and illumination characteristic data is obtained at block  618 . Any or all of this data is used to generate optimized image capture settings at block  622 , and these settings are implemented as image capture settings for the device at block  624 . A baseline image capture is made at block  628 . In the event that no presetting is to occur, progress is made directly from block  606  to block  628 . 
         [0028]    After a baseline image has been captured at block  628 , the associated data is stored at block  632  and a determination is made at block  636  as to whether a new image should be captured. This may be determined, by way of example, by passing of a preselected duration from a prior image capture. If a determination is made that a new image should not yet be captured, a test for possible tuning or re-tuning is made at block  660 . If so, image capture settings are tuned at block  664  and illumination settings are tuned at block  668 . These new settings are implemented at block  670 , and progress returns to block  636  to determine if it is time for the next imaging operation. 
         [0029]    If, at block  636 , a new image should be captured, then progress is made to block  640  and an image is captured. Progress is then made to block  642  where the captured image is compared to the baseline image. Progress is then made to block  644  where comparison data is generated based on the compare operation of block  642 , and in block  650  a determination is made as to whether to transmit the data. If so, the data is wirelessly transmitted in block  652  and progress returns to block  636  to await the next imaging operation. If not, then progress returns to block  636  without wireless transmitting the data. 
         [0030]      FIGS. 7-9  illustrate graphically example embodiments certain of the characteristics in connection with the description above.  FIG. 7  shoes a relationship of oxytocin concentration with reflected or luminescent light from tissue. By way of example, light of interest may be in the 405 nm range.  FIG. 8  shows a time lapse of disease progression as determined by a sequence of image captures as detailed above.  FIG. 9  shows brain deterioration by measured values relative to established values of a normal population. The shaded area indicating early deterioration levels that current art CT, MRI, and ultrasound typically fail to detect. These relationships are suitably used to detect one or more maladies in a subject into which a biosensor has been implanted. 
         [0031]    While certain embodiments have been described, these embodiments have been presented by way of example only, and are not intended to limit the scope of the inventions. Indeed, the novel embodiments described herein may be embodied in a variety of other forms; furthermore, various omissions, substitutions and changes in the form of the embodiments described herein may be made without departing from the spirit of the inventions. The accompanying claims and their equivalents are intended to cover such forms or modifications as would fall within the spirit and scope of the inventions.