Patent Description:
This invention was made with government support under R15-CA119253, awarded by the National Institutes of Health. The government has certain rights in the invention.

Existing diagnostic imaging techniques of breast cancer include X-ray mammography, computer tomography (CT), ultrasound, magnetic resonance imaging (MRI), and nuclear imaging. <FIG> illustrates a table summarizing the advantages and disadvantages of each existing diagnostic imaging process or technique. These conventional techniques may be limited by poor resolution, use of harmful ionizing radiation, lack of portability, and/or expensive instrumentation.

Diffuse optical imaging (DOI) (also known as Near-infrared (NIR) optical imaging) is an emerging non-invasive technology that may be applied towards deep tissue imaging, with one application being breast cancer diagnostics However, the existing NIR optical imaging systems may be limited in a number of ways. For example, existing NIR imaging apparatus may be large and bulky systems, and thus, not generally portable. NIR imaging apparatus may also cause patient discomfort because the apparatus may require a patient to be placed in certain positions or may require compression of patient tissue. Moreover, conventional NIR imaging apparatus and methods may be limited to imaging only fixed volumes or certain shapes of breast tissue. In recent years, hand-held probe based optical imaging systems have been developed for clinical applications. These hand-held probe based systems represent an alternative to the conventional bulky optical imaging systems. However, the available hand-held optical imagers employ contact imaging that is impractical for many applications (e.g., surgical settings, imaging of open wounds, etc.), require multiple probes, and/or are incapable of performing both trans-illumination and reflective imaging. For example, <CIT> discloses such a hand-held probe based NIR optical imaging system.

An imager includes an assembly forming a hand-held probe. The hand-held probe includes a probe body and a detector assembly that includes a detector operable to capture a focused, non-point image in the near infrared spectrum. The probe also includes a source assembly including near infrared light source, and a tracking target. The near infrared light source is movable relative to the detector such that the probe can perform both reflectance and trans-illumination measurements. In addition to the assembly forming the hand-held probe, the imager includes a processor configured to capture image data from the detector assembly and to co-register the image data with a 3D mesh.

<FIG> illustrates general principles behind an optical imaging process. Light <NUM> from a source <NUM> is projected on a target tissue <NUM> at a wavelength in the NIR spectrum. The tissue <NUM> may minimally absorb the light <NUM> while reflecting and scattering a majority of the light. A corresponding light detector <NUM> may be positioned to measure characteristics of the reflected light <NUM>, such as intensity, phase, or time delay.

Generally, when NIR light is launched onto a tissue surface, light propagates into the tissue and is minimally absorbed (in biological tissues, hemoglobin and water are least absorbent in the near-infrared spectrum) and preferentially scattered, allowing deep penetration of the light into the tissue and providing an opportunity for diagnostic imaging. The reflected light and/or trans-illuminated light (i.e., light that enters tissue at a first surface and exits the tissue at a second surface opposite the first surface) may be collected at a set of point locations or by an imaging device (e.g., a charge-coupled device) on or near the tissue surface. From the collected reflected or trans-illuminated measurements, images of scattering (µs) and absorption (µa) coefficients of the entire tissue domain may be generated using appropriate light propagation models and reconstruction algorithms (discussed further below). Diffuse optical imaging enables translation of the highly scattered light signals into clinically meaningful information about human tissue. For example, optical properties may be used to locate and identify physiological changes in the tissue that may indicate the existence and/or location of tumors.

Differences in composition of the tissue may cause a difference in the light characteristics (e.g., in terms of reflected/trans-illuminated light intensity, phase, time delay, etc.) of the imaging data collected. This difference in light characteristics may be used to determine abnormal tissue growth. For example, optical imaging may be used to detect a breast tumor in a chemical environment by looking for two intrinsic cancer signatures: increased blood flow (as shown by the total hemoglobin concentration) and hypermetabolism (as shown by a drop in oxygen concentration). As illustrated in <FIG>, when NIR light <NUM> encounters an angiogenic (growth of blood vessels from surrounding tissue to solid tumors) region <NUM> of a breast tissue <NUM>, light may be absorbed based on the different concentrations of hemoglobin in that area of the breast, thus providing endogenous contrast between normal and tumor tissue. The difference in light characteristics of the collected diffused light <NUM> may reflect the difference in absorption and/or scattering arising from this angiogenic region <NUM>.

To detect tissue features (such as lesions, blood flow, etc.) smaller than about <NUM> (in diameter), and/or tissue features deeper within the tissue, external contrast agents may need to be used in order to improve the optical contrast between normal and diseased tissues in a process known as fluorescence-enhanced optical imaging. Fluorescence-enhanced optical imaging involves the administration of exogenous fluorescent contrast agents that specifically bind to target tissue (e.g., tumor tissue) and that are excitable in the NIR wavelength range. The external fluorescent contrast agents molecularly target the metastatic cancer cells within the breast tissue and enhance the optical contrast between the cancerous cells and the background breast tissue.

<FIG> illustrates a fluorescence-enhanced optical imaging process. In a fluorescence-enhanced optical imaging process, a target-specific florescent contrast agent <NUM> may be injected into the tissue <NUM>. When NIR light <NUM> is launched at the tissue surface <NUM>, the minimally-absorbed and preferentially-scattered excitation photons propagate deep into the tissue <NUM>. Upon encountering a fluorescent molecule <NUM> (e.g., found at the site of target tissue substructure), the photons excite the fluorescent molecule <NUM> from its ground state to a higher orbital level. After residing at the higher energy orbital for a period (known as the fluorescence lifetime), the fluorescent molecule emits a fluorescent signal <NUM> at a greater wavelength than the incident NIR light <NUM>. The emitted fluorescent signal <NUM> along with the attenuated excitation signal <NUM> (which is at the same wavelength as the incident light) propagates back through the tissue surface where it is detected. At a detection site or device (not shown in <FIG>), appropriate optical filters may be used to separate the fluorescence signal from the attenuated excitation signal to provide relevant light characteristic data. <FIG> depicts the NIR light <NUM> as a modulated signal (i.e., implementing a frequency-domain analysis), however the analysis may be conducted in the time domain, in the frequency domain, or in a continuous wave implementation.

Three distinct measurement techniques may be used to process the collected light characteristic data in optical imaging. These techniques include continuous wave, time-domain photon migration (TDPM), and frequency-domain photon migration (FDPM) based imaging. Each of these measurement techniques has advantages and disadvantages, and the selection of the appropriate technique largely depends on the specific application and requirement.

Continuous wave (CW) measurement technique uses steady state light of constant intensity on the tissue surface and measures the attenuated intensity of the trans-illuminated and/or reflected light. In continuous wave based fluorescent optical imaging the NIR light attenuates due to absorption and scattering in the tissue medium. Upon encountering the florescent molecule, a steady state florescent signal is emitted, which attenuates before it is detected at the tissue surface. Continuous wave-based imaging instrumentation is relatively simple and involves low-cost optical components. The major disadvantages of continuous wave measurement technique include difficulty in resolving tissue absorption from scattering and inability to image the fluorescence decay kinetics. When independent measurements of tissue optical properties (i.e. absorption, scattering or fluorescence lifetime) and/or depth information are required, the use of TDPM or FDPM measurement techniques may be necessary.

TDPM measurement techniques illuminate tissue with ultra fast (e.g., in the femtosecond to picosecond time range) photon pulses and resolve the arrival of the photons as a function of time at different locations around the tissue boundary. In a TDPM-based fluorescence optical imaging process the excitation light pulse broadens and attenuates as it travels through the scattering medium. Upon encountering a fluorescent molecule, a fluorescent light pulse is emitted, which broadens and attenuates as it propagates in the tissue medium. This broadened pulse of fluorescent light is further broadened and attenuated due to absorption and scattering in the tissue medium, before it is detected at the tissue surface using, for example, fluorescence optical imaging.

The TDPM measurement technique may provide better depth information compared to a continuous wave measurement technique. Although TDPM-based measurements provide a wealth of information that may be used to map optical properties of tissues, TDPM measurement techniques may be limited by their large signal-to-noise ratio (SNR) range, which may require significant data acquisition times compared to CW and FDPM measurement techniques.

In FDPM-based fluorescence optical imaging, modulated excitation light is launched onto the tissue surface and the modulated fluorescent signal is detected at the tissue surface in terms of amplitude and phase shift. Measurements of the light intensity and the phase shift of the photon wave-front are obtained with respect to the source light information about the tissue optical properties and fluorochrome distribution. Frequency domain measurement technique may be preferable over TDPM measurement technique due to its inexpensive instrumentation. In addition, the steady-state FDPM measurements in terms of amplitude and phase shift are minimally corrupted by ambient light, since the instrument detects only a modulated signal. Thus, the FDPM instrument automatically acts as a filter for ambient light rejection, which is an advantage of FDPM measurement techniques over continuous wave or TDPM measurement techniques. However, FDPM measurement techniques require frequencies of several hundred MHz or higher to achieve depth information that may be difficult to obtain using continuous wave technique. In practice, usually a single frequency may be employed, and the phase shift may be used to estimate the mean time of flight of the photons. However, data obtained at multiple frequencies may improve FDPM imaging performance and may be equivalent to TDPM data via the inverse Fourier Transform.

While some embodiments are described as implementing fluorescence-based imaging, it should be understood that any of the embodiments herein may implement imaging with or without fluorescence and, in particular, may implement NIR imaging in addition to, or instead of, fluorescence based imaging.

NIR-based imaging approaches, whether based on endogenous or exogenous contrast, involve trans-illumination and/or reflection measurements. These measurements represent the light propagation between light sources and detector sensor pairs, and are based on excitation illumination and excitation/emission detection. Generally, trans-illumination is the shining of a light through a target tissue, such as breast tissue, to observe the absorption pattern from a different surface of the tissue medium. Reflection measurements involve observing light reflected off a tissue surface from the same side as the incident light.

Generally, existing optical imaging configurations for arranging sources (for providing incident/excitation signals) and detectors (for collecting reflected and/or trans-illuminated NIR signals, fluorescence or non-fluorescence signals) may be broadly categorized into projection shadow, circular, and sub-surface/reflective configurations.

<FIG> illustrates a projection-shadow optical imaging process. Projection-shadow imaging involves collecting trans-illuminated light from the tissue object. Trans-illuminated light may refer to light that traverses a surface(s) of a tissue. In trans-illumination method, sources <NUM> and detectors <NUM> are placed on opposite sides of breast tissue <NUM>. In this geometry, single/multiple sources may be deployed on other areas of the subject tissue so that light passes through the tissue before reaching the detector(s). Optical properties of the three dimensional tissue are obtained between the source and the detector planes. This method generally requires compression of the target tissue. The compressed tissue configuration may be analogous to x-ray mammography, and may be disadvantageous due to patient discomfort caused by tissue compression and due to limited information obtained for the entire breast tissue.

<FIG> illustrates a circular imaging process, wherein both the reflected and trans-illuminated light is collected along a circular circumference of the tissue. In this configuration, multiple sources <NUM> and detectors <NUM> are disposed about the circular circumference of the tissue. The circular configuration may be minimally uncomfortable to a patient, but is limited by the bulky and non-portable size of the apparatus.

<FIG> illustrates sub-surface imaging, which may involve collecting reflected and/or trans-illuminated light using multiple sources <NUM> and detectors <NUM>. This configuration requires no tissue compression, and may be designed to mimic a hand-held imaging probe. Many known commercial optical imaging systems and hand-held probes developed using the sub-surface imaging configuration are designed to only collect reflected light using flat measurement probe heads.

While the principles above are described with reference to multiple sources and multiple detectors, the principles nevertheless also apply to area source and area detector systems.

<FIG> depicts an embodiment of a hand-held, portable and modular NIR optical imager <NUM>. A probe assembly <NUM> includes a probe body <NUM> formed as a hollow housing that contains a face <NUM> with an opening <NUM>. The probe body <NUM> has a small size (around <NUM> x <NUM> x <NUM>, in one embodiment) such that it can be easily held in the hand of an operator. Light may enter the probe body <NUM> of the probe assembly <NUM> through the opening <NUM> and propagate into a detector assembly <NUM>. The detector assembly <NUM> may be mounted on the interior of the probe body <NUM> by means of one or more rails <NUM>, and the detector assembly <NUM> may move along the rail <NUM> along an optical axis <NUM> of the detector assembly <NUM> to adjust the detection area of the detector assembly <NUM>. The detector assembly <NUM> may be held in position along the rail <NUM> by one or more pieces of fastening hardware, such as bolts <NUM> and <NUM> to maintain a fixed distance from the subject tissue and, accordingly, maintain the desired detection area. A source attachment point <NUM> is disposed on a side of the probe body <NUM> for attaching a light source assembly (not shown in <FIG>). While the source attachment point <NUM> is disposed on one side of the probe body <NUM>, toward the opening <NUM>, it should be apparent that the source attachment point <NUM> may be placed at any convenient position on the probe body <NUM>, including on the top surface. Additionally, while only one source attachment point <NUM> is depicted and described, multiple source attachment points <NUM> may be included. Where multiple source attachment points <NUM> are included, they may each be adapted to accept different light source assemblies, or may be adapted to accept similar light source assemblies. Additionally, multiple source attachment points (and the light source assemblies attached to each) may be individually controllable, and may be used simultaneously, sequentially, or individually.

In any event, both the source attachment point <NUM> and the detector assembly <NUM> are connected via one or more wires <NUM> to a communication and power module <NUM>. The communication and power module <NUM> is connected to a computing device <NUM> by a cable <NUM>. The computing device <NUM> may consist of a laptop or tablet computer, for example, and the cable <NUM> may consist of a Universal Serial Bus (USB) cable, for example. A tracking target <NUM> is mounted on the probe body <NUM> in various embodiments.

In the implementation depicted in <FIG>, the computing device <NUM> (connected to the probe assembly <NUM> via the connection <NUM>) provides control signals, provides power to the module <NUM>, the detector assembly <NUM>, and the source attachment point <NUM>, receives control signals from the module <NUM> and/or the detector assembly <NUM> and the source attachment point <NUM>, and collects data from the detector assembly <NUM>. While the use of USB power and control allows for a small portable device that is not dependent on bulky control and power boxes, any suitable physical and/or logical interfaces may be used to provide control, power, and data communication to and/or from the computing device <NUM>. For even more portability, other embodiments of the optical imager <NUM> may use a power storage unit, such as a battery (not shown), mounted in the probe assembly <NUM> for power and a wireless receiver (not shown) for control communication and data collection.

As described above, the detector assembly <NUM> is operable to move along the rail <NUM> such that the detection area at a tissue surface <NUM> is adjusted. That is, a smaller detection area results from the detector assembly <NUM> being positioned closer to the tissue surface <NUM>, and a larger detection area may result from the detector assembly <NUM> being positioned further from the tissue surface <NUM>. As will be appreciated, in some instances, adjusting the position of the detector assembly <NUM> may assist in focusing the image detected by the detector assembly <NUM>. Once the operator determines a detection area, the detector assembly <NUM> may be fixed at a single location along the rail <NUM> by the bolts <NUM> and <NUM>. The operator may adjust the bolts <NUM> and <NUM> and the position of the detector assembly <NUM> from the exterior of the probe body <NUM>. Alternatively, in some embodiments, powered actuators (not shown) may move the detector assembly along the rail <NUM>. In an example, these powered actuators are controlled via a wired or wireless connection to a laptop or tablet computer (e.g., the computing device <NUM>), for example via the module <NUM>, thus automating the adjustment of the detection area (or focusing the device). It is not required that the powered actuators be controlled by the computing device <NUM>, though; instead, the powered actuators may be controlled by one or more controls (e.g., buttons, sliders, etc.) on the probe body <NUM>. In any event, in such an automated implementation, the adjustment of the detection area may also be automatic to satisfy requirements of software or to optimize performance and increase ease of use.

In other embodiments, the detector assembly <NUM> may not be mounted on the rail <NUM>. Instead, the detector assembly <NUM> may include exterior threads (not shown) operable to threadably engage corresponding threads on the interior of the probe body <NUM> or, alternatively, on the interior of an intermediary body (not shown) between the detector assembly <NUM> and the probe body <NUM>, such that rotating the detector assembly <NUM> relative to the probe body <NUM> (or the intermediary body) moves the detector assembly along the axis <NUM> to adjust position and/or focus.

The tracking target <NUM> allows the 3D position of the probe assembly <NUM> and, in particular, the data collected by the probe assembly <NUM>, to be coregistered with the image data captured by the detector assembly <NUM>. In various implementations, the tracking target <NUM> may comprise one or more light emitting diodes (LEDs) that are tracked by an external, stationary external tracking device (not shown). This external tracking device may be a portable tracker that is mounted on a stand, such as a camera tripod. In other implementations, the tracking target <NUM> may consist of an acoustic tracking target <NUM> and/or an electromagnetic target (if the remainder of the probe assembly <NUM> does not include metallic parts) and/or it may comprise various kinematic sensors such as a gyroscope, accelerometer, and compass. This may be particularly useful in applications where the available space or existing light conditions do not allow for optical tracking.

The exemplary optical imager <NUM> illustrated in <FIG> is modular and may function with a variety of fixed or movable light source assemblies. For example, the operator of the optical imager <NUM> may easily attach a light source assembly designed for reflectance measurements, or the operator may attach a light source assembly designed for adjacent or trans-illumination measurements. Moreover, different light source assemblies may include light sources of differing wavelengths, intensities, polarizations, etc. may be easily exchanged, and light source assemblies may include various optical elements (such as lenses, diffusers, collimators, filters, expanders, etc.,) allowing for extreme customization of the light source assembly to fit the particular needs and/or desires of the operator. Still further, light source assemblies according to the various embodiments described herein may include a single light source (e.g., a single LED) or a multiplicity of light sources (e.g., an array of LEDs). Where the light source assembly includes a single light source (or, in fact, multiple light sources), a light source operable to emit multiple wavelengths (individually or concurrently) may be used. Where the light source assembly includes more than one light source, the multiple light sources may be the same (i.e., to provide greater light intensity), may be different (i.e., may be different wavelength light sources), or may be a combination of same and different light sources. In this way, the imager <NUM> can access a wealth of optical data without sacrificing portability and convenience. The modular design also lets users expand the functionality over time or as needed in the clinical application.

While <FIG> depicts the exemplary optical imager <NUM> described above, the optical imager <NUM> may be modified in any of a variety of ways. For example, in an embodiment, the communication and power module <NUM> may not be incorporated within the probe assembly <NUM> of the optical imager <NUM> and, instead, may take the form of an external control module (not shown). The external control module may perform the same functions as the communication and control module <NUM> described above, including serving as a communication interface between the detector assembly <NUM> and the source attachment point <NUM>, and the computing device <NUM>. The external control module may also provide power to the detector assembly <NUM> and to the source attachment point <NUM>.

In still other embodiments, either the external control module or the communication and power module <NUM> may also function as the computing device <NUM>, eliminating the need for an external computer and providing sufficient control, command, and processing power to control the device and thereby providing additional portability and convenience to the operator. In one or more of these embodiments, a display may be included and, for example, integrated with the control box or the communication and power module <NUM> to compensate for the loss of the display that would otherwise have been included in the computing device <NUM>.

As will be appreciated from the examples above, the power source may likewise be incorporated into the optical imager <NUM> in various manners. As described above, power for the optical imager <NUM> and its various components may be provided by the computing device <NUM>, or by a battery located elsewhere. In some embodiments, the power source is incorporated in the communication and power module <NUM> as a battery or as a connection to a power main. Likewise, in some embodiments, a small, separate mainline power supply or a battery may be incorporated within or attached to the probe body <NUM> of the probe assembly103.

The optical imager <NUM> may likewise, in various embodiments, incorporate a wireless interface. For example, in a particular embodiment, the probe assembly <NUM> includes the communication and power module <NUM>. The communication and power module <NUM> may include a battery for providing power to the remainder of the optical imager <NUM>, or may include a coupling mechanism for coupling the communication and power module <NUM> to a separate power source (e.g., to an external battery, to a power main, etc.). In such embodiments, the communication and power module <NUM> may include a wireless interface for communicatively coupling the optical imager <NUM> to an external computer (not shown). The wireless interface may be any interface appropriate for the purpose including, by way of example and without limitation, Bluetooth®, IEEE <NUM>. 11a/b/g/n/ac, mobile telephony, etc. In any event, the external computer to which the optical imager <NUM> is coupled may serve as a control computer, or may merely be used to receive data wirelessly from the optical imager <NUM> after the diagnostic imaging is complete. In fact, there is no reason why any embodiment of the optical imager <NUM> or the probe assembly <NUM> specifically could not include a wireless communication interface for connecting to an external computer, the computing device <NUM>, or any other device (e.g., remote storage, cloud storage, other diagnostic devices, etc.).

<FIG> illustrates an example implementation, which is not part of the claimed invention, of a fixed light source assembly <NUM> designed for reflectance imaging. The fixed light source assembly <NUM> is attached to the probe body <NUM>, as depicted in <FIG>, at the source attachment point <NUM>. The probe body <NUM> houses the adjustable detector assembly <NUM>. The light propagating from the fixed light source assembly <NUM> is projected on the target tissue surface <NUM> and, after being scattered and/or attenuated in the target tissue surface <NUM>, is reflected towards the detector assembly <NUM>. The reflected light passes through the opening <NUM> and into the detector assembly <NUM>. The attached fixed light source assembly <NUM> is not capable of trans-illumination imaging, but it may allow for slight adjustments of the light source assembly <NUM>. For example, the source attachment point <NUM>, may comprise a bolt or pin that allows the light source assembly <NUM> to pivot. A ring or collar (not shown) on the body, to which the attachment point <NUM> is coupled, may allow the light source assembly <NUM> to rotate around the probe body <NUM> and the detector assembly <NUM>. The operator of the device may thus pivot and/or rotate the fixed light source assembly <NUM> to modify the angle at which the light is incident on the tissue surface <NUM>.

<FIG> illustrates an example implementation of a tethered light source assembly <NUM> designed for reflectance, adjacent, or trans-illumination imaging. The tethered light source assembly <NUM> is attached to the probe body <NUM> at the source attachment point <NUM>. A flexible piping <NUM> extends between a coupling end <NUM> that connects the light source assembly <NUM> to the probe body <NUM> at the attachment point <NUM> and a light source module <NUM> that includes a light source and any optical components. The flexible piping <NUM> (which is not intended to be limited to any particular structure) is such that the light source assembly <NUM> may be positioned for reflectance, adjacent, or trans-illumination imaging. In some embodiments, the flexible piping <NUM> may be semi-rigid such that the light source assembly <NUM> and, in particular, the light source module <NUM>, is moveable but remains in a desired position when placed in the position. The semi-rigid design frees the operator's hand that would, otherwise, necessarily have to hold the light source module <NUM> in place during imaging. Alternatively, the flexible piping <NUM> may be flexible enough that it does not maintain its position, which may facilitate maximum flexibility and/or positionability. As yet another alternative, the flexible piping <NUM> may be a segmented piping, such as the widely available ball-and-socket type coolant pipe.

In any event, the probe body <NUM> may include an anchor point <NUM> (in addition to the source attachment point <NUM>) operable to receive the light source module <NUM>. The anchor point <NUM> may provide a resting position for the light source module <NUM> when it is not in use. Additionally, in some embodiments, the anchor point <NUM> may be coupled to the probe body <NUM> by a pin and/or ring (as described above with respect to <FIG>) that may allow the light source module <NUM> to pivot and/or rotate, respectively, when the light source module <NUM> is placed in the anchor point <NUM>. In this manner, the light source assembly <NUM> may operate as in a manner similar as the light source assembly <NUM> when the light source module <NUM> is placed in the anchor point <NUM>.

The flexible piping <NUM> may contain wires which may couple the light source module <NUM> to the communication and power module <NUM>. The wires may provide power to the light source module <NUM> and/or may provide communication of control and data signals between the communication and power module <NUM> and the light source module <NUM>. The control and data signals may include, by way of example and without limitation: information about components (e.g., the light source and other optical components) in the light source module <NUM>; control signals for controlling the components in the light source module <NUM>; feedback signals from the light source module <NUM>; and the like. In some embodiments, the light source assembly <NUM> may be powered by a self-contained power supply module, such as one containing batteries, and control of the light source assembly <NUM> may be maintained via a wired or wireless connection to the communication and power module <NUM> and/or the computing device <NUM>.

In other embodiments, which are not part of the claimed invention, a fixed light source assembly may be configured for trans-illumination using compression of the subject tissue. <FIG> depicts one such embodiment. In <FIG>, a probe assembly <NUM> may include generally, the probe body <NUM> of any of the previously described embodiments, including the detector assembly <NUM> in any embodiment described above, and including a transparent solid plate <NUM> (e.g., glass or plexiglass) that is transparent to the wavelength(s) of light to be detected and covers the opening <NUM>. The probe body <NUM> may be physically coupled to an adjustable handle assembly <NUM>. The adjustable handle assembly <NUM> may be handle-shaped in that it may be designed to be held easily in an operator's hand. The shape of the handle assembly <NUM> is designed such that the covered opening <NUM> of the probe assembly <NUM> is generally parallel to an opening <NUM> through which light from a source assembly <NUM> is output. That is, the optical axis <NUM> of the detector assembly <NUM> is generally aligned with an optical axis <NUM> of a source module <NUM> in the source assembly <NUM>. The source module <NUM> may be any embodiment of the source module generally described above.

Like the detector assembly <NUM>, the source assembly <NUM> also includes a transparent solid plate <NUM> (e.g., glass or plexiglass) that is transparent to the wavelength(s) of light to be detected and covers the opening <NUM>. The plates <NUM> and <NUM> may be approximately the same size, and may be larger than either of the corresponding openings <NUM> and <NUM>, respectively, such that they are able to compress the subject tissue between them.

The handle assembly <NUM> may have an adjustment mechanism <NUM> that facilitates adjustment of a detector portion <NUM> of the handle assembly <NUM> and a source portion <NUM> of the handle assembly <NUM> such that the probe body <NUM> and the source assembly <NUM> are movable to be closer to or further from one another, and to compress subject tissue (e.g., breast tissue) between the two for trans-illumination imaging. In the embodiment depicted in <FIG>, the detector portion <NUM> and the source portion <NUM> cooperate to create a telescoping mechanism that may be adjusted, for example, by turning a knob or, as another example, by depressing a release plunger to allow one portion to slide into and out of the other. While the handle assembly <NUM> is depicted in <FIG> as having squared off corners, in other embodiments, the handle assembly <NUM> may be completely rounded.

In some embodiments, the handle assembly <NUM> is modular and detachable from the probe body <NUM> connecting to the probe body <NUM>, for example, at the source attachment point <NUM>.

<FIG> illustrate example applications of the modular optical imager <NUM> with the light source assembly <NUM>, for reflection, adjacent, and trans-illumination imaging, respectively. The ability to use the currently disclosed imager with a variety of imaging techniques is a great advantage compared with existing hand-held and, in particular, fiber-free hand-held, imagers that are limited to reflection or trans-illumination individually. As such, operating costs can be reduced by the need for only one simple and modular imager as compared with multiple imagers for multiple applications. In addition, the ability to use a single, portable device to perform both trans-illumination and reflectance imaging is preferable over carrying a multiplicity of different devices to achieve the same flexibility.

Example fixed and tethered light source assembly attachments <NUM> and <NUM> have been illustrated in <FIG>, but other modular attachments or combinations of modular attachments may be used along with the probe body <NUM>. For example, a combination of the fixed light source assembly <NUM> and the tethered light source assembly <NUM> may be implemented for illuminating the target from multiple directions simultaneously. Alternatively, two light source assembly attachments that operate at differing wavelengths may be implemented to obtain a greater range of optical data, as well as physiologically meaningful data such as oxy-hemoglobin (HbO), deoxy-hemoglobin (HbR), and total hemoglobin (HbT). A single probe assembly may be acquired for a clinical application with only the needed modular attachments, and other attachments may be acquired over time or as needed.

<FIG> depicts an exemplary implementation of a probe assembly <NUM> illustrating the components of the detector assembly <NUM>. In the probe assembly <NUM> the detector assembly <NUM> is mounted inside the probe body <NUM> on the rail <NUM>. The detector assembly <NUM> is movable along the rail <NUM> and may be held stationary by the bolts <NUM> and <NUM>. The detector assembly <NUM> is communicatively coupled via one or more wires <NUM> carrying signals to and/or from the communication and power module <NUM>. In the probe assembly <NUM>, the detector assembly <NUM> includes a charge-coupled device (CCD) <NUM>, and may include a lens assembly <NUM>, a focusing lens <NUM>, and/or an optical filter <NUM>. Light enters the probe body <NUM> through the opening <NUM> and then enters the detector assembly <NUM>. The light entering the detector assembly <NUM> passes through the optical filter <NUM>, the focusing lens <NUM>, the lens assembly <NUM>, and falls incident upon the CCD <NUM>. In some embodiments, the opening <NUM> may be covered with a solid plate <NUM> (e.g., glass or plexiglass) that is transparent to the wavelength(s) of light to be detected. The transparent solid plate <NUM> may be useful when a flattened tissue surface is desired for imaging.

The CCD <NUM> is optimal for detecting with high resolution reflected, adjacent, or trans-illuminated light over an area <NUM>. As will be readily appreciated, moving the detector assembly <NUM> along the rail <NUM> will adjust the detection area <NUM>, making it smaller or larger as the detector assembly <NUM> is moved, respectively, toward or away from the subject tissue. Existing fiber-based imaging systems have a limited spatial resolution (owing to the fact that each detection fiber is a point detector) and become more complicated and expensive as the number of fibers increases to increase resolution. By using a CCD to directly image the tissue surface, the complexity, size, and cost associated with the optical fibers and the attendant equipment is eliminated. Moreover, in contrast to devices employing fiber-optic point detection, the presently described device is not only more portable, but useful for a variety of applications for which previous imaging devices were not useful, including: field applications, non-contact imaging applications, and the like.

The exemplary CCD <NUM> captures images with high NIR sensitivity, high spatial resolution (<NUM> x <NUM> pixels, for example), and a high frame rate (<NUM> frames per second, for example). Other CCDs or devices substituted for the CCD <NUM> may have other properties according to the desire of the user, and the modular design of the imager <NUM> provides swapability (i.e., the ability to quickly exchange one component for another) to allow for replacement of a damaged component or exchange of one component for another. Data corresponding to the image detected by the CCD <NUM> are transferred, via the wires <NUM>, through a connector (which may be housed in the communication and power module <NUM>) to a low-cost frame grabber. The frame grabber may be part of the communication and power module <NUM> or it may be part of the computing device <NUM>. In any event, the frame grabber converts the analog image signal output from the CCD <NUM> into digital data, for example, by implementing, among other things, an analog to digital converter (ADC). The digital data may then be processed by one or more hardware and/or software modules on the computing device <NUM>. Alternatively, the CCD <NUM> may include an on-board frame grabber. In such an embodiment, the data from the CCD <NUM> may be directly processed in the computing device <NUM>.

Referring still to <FIG>, the lens assembly <NUM> contains one or more lenses <NUM>. The lenses <NUM> may be replaced or exchanged depending on the clinical application. In some implementations, the lenses <NUM> include a combination of converging and diverging lenses such that a focused image of the detected area <NUM> is formed on the CCD <NUM>. In other implementations, the lenses <NUM> include a combination of converging and diverging lenses such that the image of the detected area <NUM> is magnified. The software that analyzes the data from the detector assembly <NUM> may be optimized for a certain image orientation and/or magnification, and the lenses <NUM> in the lens assembly <NUM> may be used to provide the software with the expected types of data.

In addition to the light propagating through the lens assembly <NUM> and onto the CCD <NUM>, the light may pass through the focusing lens <NUM> and/or the optical filter <NUM>. The focusing lens <NUM> focuses the raw light that is reflected by or transmitted through the target tissue. The light entering the detector assembly <NUM> may be very diffuse and/or very attenuated. The focusing lens <NUM> gathers this light and guides it into the other optical elements (such as the lens assembly <NUM>) of the detector assembly <NUM>. The optical filter <NUM> conditions the light such that the CCD <NUM> and software can appropriately process the signal. For example, absorptive filters may only pass light of a certain wavelengths and other filters may align the polarization of the incident light. Using such a filter, radiation that might cause the CCD <NUM> to malfunction can be eliminated and interfering signals (such as the signal from the NIR source) can be removed, or such a filter might allow the for specialized analysis. In some embodiments, multiple filters may be used to fine tune the properties of light incident on the CCD <NUM>, such as by separating the emission signal from the attenuated excitation signal, or attenuating a high intensity detected signal.

Of course, the optical elements <NUM>-<NUM> need not be arranged in the order depicted in <FIG> and described above. In some embodiments, for example, the focusing lens <NUM> may be optically adjacent (i.e., the first element from) the CCD <NUM>. In other embodiments, the focusing lens <NUM> may be an integral part of the CCD <NUM> (e.g., when the CCD <NUM> is a camera assembly).

Referring now to <FIG>, a particular optional aspect of the imager <NUM> is depicted. Specifically, in some embodiments, a slot <NUM> in the side of the detector assembly <NUM> and/or a slot <NUM> in the probe body100 allows the operator of the optical imager <NUM> to add or exchange optical elements, including in various embodiments, the CCD <NUM>, the lens assembly <NUM>, the filters <NUM>, and/or the focusing lens <NUM>. That is, the operator may be able to add or exchange a component without disassembling the probe body <NUM> (through the slot <NUM> in the probe body). If the component in question is within the detector assembly <NUM>, a corresponding slot <NUM> in the detector assembly <NUM> may allow the operator to add or exchange the component in the detector assembly <NUM>. In some embodiments, each replaceable/exchangeable component has a slot <NUM> in the detector assembly <NUM>, and the detector assembly <NUM> may be moved within the probe body <NUM> such that the slot <NUM> for each particular component may be aligned with the slot <NUM> in the probe body <NUM>. In still other embodiments, one or more of the components may be part of a component cartridge <NUM> that may pass through the slot <NUM> and into the slot <NUM> such that an integrated slot cover <NUM> covers or fills the slot <NUM>, blocking external light from entering the detector assembly <NUM>.

The ability to add or exchange optical elements accommodates various imaging modalities without the need to disassemble the probe body <NUM> and/or the detector assembly <NUM> or purchase a separate detector assembly. In addition, access to the optical elements through the slots <NUM>, <NUM> opens the possibility of imaging with a variety of imaging modalities in quick succession, thus reducing the necessary time for some exams.

In some embodiments, an additional slot (not shown) in the side of the probe body <NUM> and/or in the side of the detector assembly <NUM> allows the operator to perform manual focusing of the image on the CCD <NUM>.

In contrast to fiber-based detectors, the detector assembly <NUM> depicted in <FIG> can operate with or without contacting the target tissue. The probe body <NUM>, and thus the detector assembly <NUM>, can be moved by hand towards or away from the tissue surface <NUM>. This flexibility of use has unique advantages. First, the detected area <NUM> and/or focus of the CCD <NUM> may be adjusted in real-time by moving the probe body <NUM> closer to or further from the tissue surface <NUM> (in addition to adjustments made by moving the detector assembly <NUM> along the rail <NUM>). Second, the disclosed imager <NUM> may be used in surgical setting, or in any setting in which inflamed or wounded tissue is present, where making contact with tissue is not an option. As such, the imager <NUM> may be used for pre-operative, intra-operative, and post-operative imaging applications without the need to modify the imager <NUM> or purchase specialized imaging systems.

<FIG> illustrates an embodiment of a light source module <NUM>, which may be included in or as the light source assembly <NUM> in <FIG> or may be included as the light source module <NUM> in <FIG>. The light source module <NUM> may be fixedly or semi-rigidly attached to the probe body <NUM>, as depicted in, for example, <FIG>. Alternatively, the light source module <NUM> may be coupled to the probe body <NUM> as the light source module <NUM> of the light source assembly <NUM> in <FIG>. The light source module <NUM> includes a light source <NUM>, and may additionally include one or more of: optical filters <NUM>, a collimation package <NUM>, and a beam expander <NUM>. The light emitted by the light source <NUM> propagates through the optical filters <NUM>, the collimation package <NUM>, and the beam expander <NUM> before exiting the light source module <NUM> via an opening <NUM>. In <FIG>, the light source <NUM> is depicted as an LED and, accordingly, the present description describes the light source <NUM> in terms of an LED. However, it should be understood that other light sources may be substituted for the LED in various embodiments of the claimed methods and apparatus.

In an embodiment, the light source <NUM> is an LED providing NIR light having a wavelength of <NUM>-<NUM>. In another embodiment, the light source <NUM> is an LED providing NIR having a wavelength between <NUM> and <NUM>. As described above, the light source <NUM> may be a single LED, multiple LEDs, an array of LEDs, etc. Multiple LEDs may be a single wavelength or multiple wavelengths. The LED may be driven by a driver circuit operable to control the current flow. For example, current flow to the light source <NUM> may be driven between <NUM> and <NUM> mA in one embodiment, using a variable resistor. For some applications an alternate light source may be preferred. In some embodiments, for example, the light source <NUM> in the light source module <NUM> may be modular to allow other light sources, for example a laser source, to be exchanged for the present source (e.g., the LED) without exchanging or disturbing other optical elements (e.g., the filters, collimation package, and beam expander). In other embodiments, the operator may exchange the entire light source assembly, such as the light source module <NUM>, for a different light source assembly that includes a different light source (laser, etc). The operator may also choose to image a single target with a variety of light sources.

In a manner similar to the detector assembly <NUM>, the light source module <NUM> may be mounted on a rail within (or threadably engaged with) the light source assembly <NUM>, such that the area upon which the light is incident may be adjusted by moving the LED <NUM> closer to or further from the target tissue surface.

The light source module <NUM> may be physically and communicatively coupled to the computing device <NUM> and, in some embodiments, is coupled to the computing device <NUM> through the communication and power module <NUM>. Of course, functionality of the computing device <NUM> and/or the communication and power module <NUM> may be included in a single on-board module (e.g., in the module <NUM>) or in an external control box. Control of the light source module <NUM> (and detector assembly <NUM>) by the computing device <NUM> allows the probe assembly <NUM> to maintain, at most, only one external connection. With a minimal number of external connections, the probe assembly <NUM> is easy to maneuver, especially in clinical applications where space is restricted. Alternatively, the light source module <NUM> may operate via a driver circuit (not shown) using a variable resistor to control current flow. This driver circuit may be housed in the control box or inside the probe body <NUM>.

In the embodiment depicted in <FIG>, light emitted from the source <NUM> passes through the optical filters <NUM>. The optical filters <NUM> may comprise absorptive or polarizing filters similar to those discussed in reference to the detector assembly <NUM>. In addition, a diffusing filter may scatter or "soften" the light incident from the source <NUM>. The collimation package <NUM> may fully or partially align the direction of propagation of light exiting the optical filters <NUM>. The beam expander <NUM> expands the cross-sectional area of the beam of light exiting the collimation package <NUM> to a predefined width. In one implementation, the beam expander <NUM> and collimation package <NUM> are adjustable such that the beam width and amount of collimation can be adjusted before, during, and/or after imaging. This adjustment may be a manual internal adjustment or may be performed automatically according to an external control signal received from the communication and power module <NUM> or the computing device <NUM>. One or more signals may originate at the light source module <NUM> indicating to the communication and power module <NUM> and/or the computing device <NUM> the precise components included in the optical path of the light source module <NUM>. Signals originating at the light source module <NUM> may also include feedback signals from the components of the light source module <NUM> or from components not previously described. For example, in an embodiment, the light source module <NUM> includes one or more light sensors (not shown) that detect light emitted by one or more of the components, and provides feedback to the communication and power module <NUM> and/or the computing device <NUM>. In an embodiment, an optical power meter (e.g., the PM <NUM> from Thorlabs) with a silicon sensor (e.g., the S121B from Thorlabs) may validate the stability of the light source <NUM> and provide the feedback to the computing device <NUM>.

Likewise, one or more control signals may originate at the computing device <NUM> and/or the communication and power module <NUM> to control the light source module <NUM> and its output. For example, exemplary control signals may allow perform any of the following tasks manually or automatically: providing to or withdrawing power from the light source <NUM>, adjusting power to the light source <NUM>, adjusting a controllable property of the optical filters <NUM> and/or the collimation package <NUM>, adjusting the properties of the beam expander <NUM> to increase or decrease the beam width, and the like.

<FIG> illustrates a light source assembly <NUM> with one or more optical elements <NUM> on a rotary dial <NUM>. In an embodiment, the optical elements <NUM> comprise a variety of light sources with differing wavelengths, including, in at least one embodiment, a white light source. By operating the rotary dial <NUM>, different light sources may be placed into operation and, thereby, the operator of the optical imager <NUM> may easily change the wavelength of incident light. As will be appreciated, simple substitution of one light source for another to facilitate imaging at varying wavelengths is advantageous for various clinical applications, and because it eliminates the need to carry multiple wavelength light source modules or more than one imaging device. In various other embodiments, optical filters, beam expanders, and/or other optical elements may be disposed on rotary dials such that the elements are easily exchanged. Of course, similar arrangements may be used with the detector assembly <NUM> and, in particular, rotary dials may provide an easy means for exchanging light sources <NUM>, lens assemblies <NUM>, focusing lenses <NUM>, and/or filters <NUM>.

Similar to the detector assembly <NUM>, the light source module <NUM> may be used in both contact or non-contact imaging applications. Moreover, if an tethered light source assembly, such as the tethered light source assembly <NUM>, is employed, the operator may choose to use a combination of contact and non-contact imaging when appropriate. The detector assembly <NUM> may be placed in contact with the tissue surface while the light source module <NUM> is not in contact with tissue surface, or the light source module <NUM> may be placed in contact with the tissue surface while the detector assembly <NUM> is not in contact with the tissue surface. This flexibility may be convenient when imaging hard to reach areas or when a patient in unable to optimally position herself.

<FIG> is a block diagram depicting an embodiment <NUM> of a hand-held optical imager with 3D tracking facilities. <FIG> depicts a logical view of a computing device in the form of a computer <NUM> that may be used in such a system (e.g., as the computing device <NUM>). For the sake of illustration, the computer <NUM> is used to illustrate the principles of the instant disclosure. However, such principles apply equally to other electronic devices having sufficient computing power, including, but not limited to, cellular telephones, smart phones, tablet computers, netbook computers, workstations, and personal digital assistants, to name a few. Components of the computer <NUM> may include, but are not limited to a processing unit <NUM>, a system memory <NUM>, and a system bus <NUM> that couples various system components including the system memory <NUM> to the processing unit <NUM>. The system bus <NUM> may be any of several types of bus structures including a memory bus or memory controller, a peripheral bus, and a local bus using any of a variety of bus architectures. By way of example, and not limitation, such architectures include Industry Standard Architecture (ISA) bus, Micro Channel Architecture (MCA) bus, Enhanced ISA (EISA) bus, Video Electronics Standards Association (VESA) local bus, and Peripheral Component Interconnect (PCI) bus, front side bus, and Hypertransport™ bus, a variable width bus using a packet data protocol.

Computer <NUM> may include one or more serial, parallel, wireless, or other communication interfaces <NUM>, such as Universal Serial Bus (USB) interfaces, IEEE-<NUM> (FireWire) interfaces, RS-<NUM> interfaces, RS-<NUM> interfaces, RS-<NUM> interfaces, IEEE-<NUM> (HPIB or GPIB) interfaces, mobile terrestrial interfaces, IEEE <NUM> interfaces, Bluetooth® interfaces, etc. The computer <NUM> may communicate through the communications interface <NUM> with, for example, the detector assembly <NUM>, the light source module <NUM>, a 3D mesh generation assembly <NUM>, and/or a tracking system <NUM> (as described in detail below).

Computer storage media includes volatile and nonvolatile, removable and non-removable media implemented in any method or technology for storage of information such as computer readable instructions, data structures, program modules or other data. Computer storage media includes, but is not limited to, RAM, ROM, EEPROM, flash memory or other memory technology, CD-ROM, digital versatile disks (DVD) or other optical disk storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, or any other medium which can be used to store the desired information and which can accessed by computer <NUM>.

By way of example, and not limitation, <FIG> illustrates operating system <NUM>, application programs <NUM> (such as one or more modules embodying part or all of the methods described herein), other program modules <NUM> (such as one or more modules embodying part or all of the methods described herein), and program data <NUM>. By way of example, the application programs <NUM> and the other program modules <NUM> may implement control of and/or cause the processor <NUM> to process data received from the detector assembly <NUM>, the light source module <NUM>, and the tracking system <NUM>. For instance, with respect to the light source module <NUM>, the programs <NUM> and modules <NUM> may implement control of the output power, etc. source <NUM>. As another example, with respect to the detector assembly <NUM>, the programs <NUM> and modules <NUM> may implement control of the CCD <NUM>, the lens assembly <NUM>, the filter assembly <NUM>, the focusing lens <NUM>, may active actuators for adjusting the position of the detector assembly <NUM> within the probe body <NUM>, and/or may process data (e.g., image information received from the probe assembly <NUM>) received from the CCD <NUM>. As yet another example, with respect to the tracking system <NUM>, the programs <NUM> and modules <NUM> may process data received from the tracking system <NUM> to determine current position and/or orientation data of the probes assembly <NUM> and/or of the subject of study, may process data received from the tracking system <NUM> and the CCD <NUM> to co-register image data and 3D mesh data, or may implement control of one or more aspects of the tracking system <NUM>. As still another example, with respect to the 3D mesh generation assembly <NUM>, the programs <NUM> and modules <NUM> may process data received from a 3D surface scanner (i.e., a scanner for generating a surface geometry or 3D mesh), may implement a control function of the 3D surface scanner, may implement control of a positioning device associated with the 3D surface scanner, etc..

The computer <NUM> may also include other removable/non-removable, volatile/nonvolatile computer storage media. By way of example only, <FIG> illustrates a hard disk drive <NUM> that reads from or writes to non-removable, nonvolatile magnetic media, a magnetic disk drive <NUM> that reads from or writes to a removable, nonvolatile magnetic disk <NUM>, and an optical disk drive <NUM> that reads from or writes to a removable, nonvolatile optical disk <NUM> such as a CD ROM or other optical media. Other removable/non-removable, volatile/nonvolatile computer storage media that can be used in the exemplary operating environment include, but are not limited to, magnetic tape cassettes, flash memory cards, digital versatile disks, digital video tape, solid state RAM, solid state ROM, and the like. The hard disk drive <NUM> is typically connected to the system bus <NUM> through a non-removable memory interface such as interface <NUM>, and magnetic disk drive <NUM> and optical disk drive <NUM> are typically connected to the system bus <NUM> by a removable memory interface, such as interface <NUM>.

The drives and their associated computer storage media discussed above and illustrated in <FIG>, provide storage of computer readable instructions, data structures, program modules, and other data for the computer <NUM>. Operating system <NUM>, application programs <NUM>, other program modules <NUM>, and program data <NUM> are given different numbers here to illustrate that, at a minimum, they are different copies. A user may enter commands and information into the computer <NUM> through input devices such as a keyboard <NUM> and pointing device <NUM>, commonly referred to as a mouse, trackball, or touch pad. Other input devices (not shown) may include a microphone, joystick, game pad, satellite dish, scanner, digital camera, or the like. These and other input devices are often connected to the processing unit <NUM> through a user input interface <NUM> that is coupled to the system bus <NUM>, but may be connected by other interface and bus structures, such as a parallel port, game port or a universal serial bus (USB). A monitor <NUM> or other type of display device is also connected to the system bus <NUM> via an interface, such as a video interface <NUM>.

The computer <NUM> may operate in a networked environment using logical connections to one or more remote computers (not depicted) over a network interface <NUM>, such as broadband Ethernet connection or other known network. The computer <NUM> may communicate via the network interface <NUM> with one or more other computers executing one or more software modules embodying a portion of the methods described herein, for example to split the processing requirements for real-time data manipulation among multiple computers.

In both modeling and image reconstruction, a region of interest(s) (e.g. <NUM>-D or 3D tissue object or phantom) may be divided into discrete <NUM>-D or 3D elements. Due to the limited detection area of the detector assembly <NUM>, sensor data are captured only for a portion of the region of interest at one time. To obtain three-dimensional visualization of a large region of interest, each time the probe assembly <NUM> is moved, the position and orientation of the probe assembly <NUM> may be monitored and co-registered or mapped. As used herein, co-registration refers to the mapping of sensor data for a particular region onto to a map (e.g., a discretized mesh) of the entire region of interest(s). Generally, registration provides 3D location and orientation data for the sensor data. For example sensor data captured during a first period at a first position of the probe assembly <NUM> may be mapped to corresponding first positions of a map of the entire region of interest. To implement self-registration or co-registration of the sensor data for the region of interest, a tracking system may be used to monitor the location of the probe assembly <NUM>.

<FIG> and <FIG> illustrate possible embodiments related to the obtaining 3D surface sensor data using a self-registering (automatic registering) hand-held probe based imaging system. <FIG> and <FIG> relate particularly to a 3D mesh generation assembly <NUM>. A three-dimensional optical scanner <NUM>, as known in the art, may be used on a target object <NUM> (without any contact) to provide a 3D surface image of the target object <NUM>, which can be volume rendered and discretized using appropriate meshing software, as known in the art. In some embodiments, the volume rendering process may involve generating a three-dimensional (3D) mesh <NUM> of point coordinates or point locations sub-surface to the rendered 3D surface image (e.g., for the entire volume of the target object <NUM>). This 3D mesh may be known as a "phantom mesh" because it serves as a structure over which the target data may be mapped or overlaid or with which the target data may be co-registered (as described below).

While not depicted in the figures, it is also possible to capture 2D images (e.g., photographs) of the target object <NUM> from multiple angles, after which the photographs may be "stitched" together by software to create a phantom geometry and, eventually, the phantom mesh.

The 3D mesh <NUM> of the target object <NUM> may be displayed on the monitor <NUM> of the computing device <NUM>. An imager <NUM> for collecting sensor data, such as the probe assembly <NUM> described above, may then be traced over the target object <NUM> to obtain sensor data. The 3D location map of the probe <NUM> with respect to the 3D mesh <NUM> of the target object <NUM> may be obtained using the tracking system <NUM> (described below). In some embodiments, the computing system <NUM> may be programmed (e.g., using appropriate software and algorithms, such as those described herein) to receive sensor data from the probes <NUM> for a time period, receive probe position data and/or orientation data from the tracking system <NUM> for the time period, and co-register the received data with appropriate mesh locations on the 3D mesh <NUM> based on the position data. In this manner, the location data and the sensor data collected over a region may be mapped to the corresponding region on the 3D mesh <NUM> surface to generate co-registered map sensor data <NUM>. The computing device <NUM> may co-register or map sensor data with respect to a reference position arbitrarily (or specifically) chosen on the 3D mesh <NUM> of the target object <NUM>. The computing system <NUM> may be further programmed to process the sensor data before and/or after mapping/co-registering to the mesh <NUM> depending on a particular application of the sensor data.

In some embodiments, the 3D mesh generation assembly <NUM> may include an automatic scanning mechanism <NUM>, such as that illustrated in <FIG>. The automatic scanning mechanism <NUM> includes a 3D surface scanner such as the 3D surface scanner <NUM> (or an image capture device) movably mounted on a positioning device <NUM>. The positioning device <NUM> may be one or more rails (such as rails 417A, 417B depicted in Figure <NUM>) upon which the 3D surface scanner <NUM> may be mounted. A motor (not shown) on the optical scanner <NUM> or integrated with the rail(s) <NUM> may position and/or move the optical scanner <NUM> from an initial position 418A, around the subject to be imaged to a final position 418C, passing through intermediate positions such as a position 418B. The optical scanner <NUM> may scan the subject continuously or, at least, a plurality of times, as it moves from the initial position 418A to the final position 418C. The positioning device <NUM> is not limited to the rails depicted in <FIG>, but instead may be a robotic arm, one or more cables, etc. In some embodiments, the movement of the optical scanner <NUM> via the positioning device <NUM> is controlled by the computing device <NUM>. The positioning device <NUM> may scan the subject at each of a plurality of heights. For example, in one embodiment, the scanner <NUM> scans the subject by moving along the rails <NUM> at a first height, and then the height of the rails <NUM> (and the scanner <NUM> mounted thereon) is adjusted and the process repeated. This process may be iterated multiple times adjusting the height of the rails <NUM> each time by, for example, <NUM> inches, <NUM> inch, <NUM> inches, etc..

Some single-probe optical imaging systems have employed acoustic trackers, which may be commercially available, to track the position of the probe head while acquiring imaging data. As described in <CIT>, entitled "Hand-Held Optical Probe Based Imaging System with 3D Tracking Facilities," and incorporated herein in its entirety by reference, acoustic trackers that determine probe location via sound may be appropriate for an optical imaging system because acoustic receivers may be small, lightweight, and inexpensive. In some embodiments, two or more acoustic trackers could be used with the dual probe head design described herein. Additionally, in some embodiments, the tracking system <NUM> (see Figure <NUM>) may employ an optical tracking method and devices or an electromagnetic tracking method and devices, instead of an acoustic tracking method and devices.

The imager <NUM> may implement in software , in hardware, or in a combination of software and hardware, various modules operable to capture and process image data. In particular, a module may implement control of the detector assembly <NUM> and, more particularly, may implement control of the CCD <NUM>. The camera control module may implement a video or image adaptor driver and the format can be searched and selected automatically.

A module may also be operable to implement image capture and processing. The image capture and processing module may provide one or more functions including, but not limited to: controlling preview mode, capturing images from the CCD <NUM>, loading image data, loading color-map data, saving color-map data, editing color-map data, implementing median filtering (a non-linear spatial digital filtering technique), implementing histogram stretching and subtraction techniques. The latter allows the operator of the imager <NUM> to investigate the specific features of a measure NIR image by, for example, interrogating histogram density and/or extracting NIR intensity information for a region of interest to investigate a change in intensity.

A module may further be operable to record video. Each module may be stored in, and may store data in, one or more computer readable memories. The video recording module may be operable to provide real-time functional imaging, for example at frame rates of <NUM> frames per second and real-time subtracted imaging.

A module, which in certain embodiments is the image capture and processing module, is operable to perform 2D target localization based on histogram thresholding. A position of a detected target is estimated by using histogram thresholding techniques to distinguish between target and background based on histogram density. While thresholding techniques have been used previously, these thresholding techniques are normally used to distinguish a target if there is a distinct boundary in the histogram data. By contrast, NIR does not have this feature, since histograms or NIR image data generally exhibit a continuous slope change in intensity. To overcome this problem, a manually determined histogram threshold criteria is employed to detect the target position by using the predetermined threshold level, <NUM> percent, for example. From the subtracted image (between background image and target image), a histogram density is first calculated and the bottom <NUM> percent of histogram intensity is used as a threshold level for histogram thresholding. A target shape and its centroid position can be extracted using the histogram thresholding method. That is, if pixel value is under the threshold value, it is regarded as a target pixel and, therefore, as part of the target area.

Utilizing data provided by the modules described above, a co-registration module may be operable to perform coregistration. A three-dimensional scanner and appropriate meshing software may be used to render a three-dimensional map (e.g., a mesh of point locations) of the target three-dimensional tissue object. Thereafter, the probe assembly <NUM> may be traced over the target tissue object. As the probe is traced over the target tissue object and sensor data are recorded from the CCD <NUM>, the position of the probe is tracked and recorded using, for example, the tracking system <NUM>. Timed sensor data may then be mapped to a location on the 3D map. In some embodiments, a computer, such as the computer <NUM> may be programmed to receive sensor data from the probe at a period of time, to receive location information from the tracking system <NUM> for the period of time, and to map this data to corresponding points on the 3D map or mesh of the target object. In this manner, a location or coordinate value is associated with the timed sensor data.

As described above, co-registration is the process of aligning image data (of a plane or volume) with other image data and/or location data within the same coordinate space. Two types of co-registration techniques exist: intermodality and intramodality. Intermodality co-registration aligns image data of different modalities, whereas intramodality co-registration aligns image data from the same modality. Intermodality co-registration is beneficial because it enables the combination of multiple images (i.e., multiple image types) such that the advantageous characteristics of each are combined into a single image, enhancing the quality of the final image. Intramodality co-registration is beneficial because it enables the alignment of image data at different locations from the same modality such that the data can be used to determine the three-dimensional location of a point of interest or to reconstruct a volume. The disclosed method and system use intramodality co-registration to obtain co-registered, three-dimensional surface images from two-dimensional surface data. Of course, as used herein, the term "real-time" does not necessarily indicate that data and/or images are updated at the same rate or greater rate as the data and/or images are received. As used herein, use of the term "real-time" indicates a lack of significant delay or lag time, and may include embodiments in which data and/or images are updated at the same rate or greater rate as the data and/or images are received. For example, the term "real-time" may indicate that an action (e.g., data processing) or event (e.g., display of an image) occurs within as much as several seconds from acquisition of the data, or may indicate that the action or event occurs within a second, or less than a second, from the data acquisition.

Co-registration of probe image data with a discretized 3D mesh mandates that the geometry of the probed 3D geometry (with which the image data is being co-registered) be known. The 3D geometry can be determined by a user's previous knowledge of the 3D geometry or by using a three-dimensional laser scanner (e.g., the 3D mesh generation assembly <NUM>), which may automatically acquire the 3D geometry. Once the tracking system <NUM> provides the locations of the probe and the NIR image data are obtained using the NIR imaging system, the image data from each probe head 100A, 100B can be co-registered onto a discretized 3D mesh at the true location of the data.

The features of the NIR imager <NUM> described above allow the imager <NUM> to automatically determine, or at least estimate, the size of a target (e.g., a tumor) and the approximate or identify the location and/or boundaries of the target within the imaged tissue. The imager <NUM> is also operable to dynamically monitor and detect blood flow changes in the tissue. At the same time, the imager <NUM> is hand-held, light-weight, ultra-portable, and drastically less expensive than previous imaging technologies. The imager <NUM> is therefore, useful in many applications (as mentioned previously) including, but not limited to: breast cancer imaging (pre-screening, pre-operative, intra-operative, and post-operative); functional brain mapping; evaluation of finger arthritis/inflammation; wound healing; concussions (including on-site evaluation); sports injuries; pressure ulcerations; or generally many deep-tissue body imaging situations requiring immediate evaluation in the field or in a clinical setting, regardless of whether contact-based or non-contact based imaging is preferred. Because of the imager's non-contact operation, the imager can be used in intra-operative applications. For example, the imager can be used to help differentiate tumor margins during breast surgeries.

Claim 1:
An assembly forming a hand-held probe comprising:
a probe body (<NUM>);
a detector assembly (<NUM>) disposed within the probe body comprising a detector operable to capture a focused, non-point image in the near infrared spectrum;
a tethered light source assembly (<NUM>) comprising a near infrared light source; and
a tracking target;
wherein the near infrared light source is movable relative to the detector such that the probe can perform both reflectance and trans-illumination measurements while the probe body is maintained in the same position.