U.S. patent application number 13/854454 was filed with the patent office on 2014-05-08 for systems and methods for computed tomographic reconstruction.
This patent application is currently assigned to University of Iowa Research Foundation. The applicant listed for this patent is University of Iowa Research Foundation. Invention is credited to Eric Hoffman, Geoffrey McLennan, Ge Wang.
Application Number | 20140128730 13/854454 |
Document ID | / |
Family ID | 32990733 |
Filed Date | 2014-05-08 |
United States Patent
Application |
20140128730 |
Kind Code |
A1 |
Wang; Ge ; et al. |
May 8, 2014 |
SYSTEMS AND METHODS FOR COMPUTED TOMOGRAPHIC RECONSTRUCTION
Abstract
An image of an object is synergistically reconstructed using two
or multiple imaging modalities. A first reconstructed image,
showing structural information of the object is produced using a
first imaging modality. The first reconstructed image is segmented,
and known optical properties of the object are then mapped to the
first reconstructed image. Optical signal emissions from the object
are detected and registered with the first reconstructed image. A
second reconstructed image volume is then produced using a second
imaging modality, based on the mapped optical properties after
registration between the first image and the data from the second
modality. The second reconstructed image depicts some optical
property, such as a bioluminescent source distribution, or optical
properties, such as, attenuation and scattering properties, of the
object.
Inventors: |
Wang; Ge; (Iowa City,
IA) ; Hoffman; Eric; (Iowa City, IA) ;
McLennan; Geoffrey; (Iowa City, IA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
University of Iowa Research Foundation |
Iowa City |
IA |
US |
|
|
Assignee: |
University of Iowa Research
Foundation
Iowa City
IA
|
Family ID: |
32990733 |
Appl. No.: |
13/854454 |
Filed: |
April 1, 2013 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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13304063 |
Nov 23, 2011 |
8428692 |
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13854454 |
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10791140 |
Mar 2, 2004 |
8090431 |
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13304063 |
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60453177 |
Mar 10, 2003 |
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Current U.S.
Class: |
600/427 ;
600/476 |
Current CPC
Class: |
A61B 6/5247 20130101;
A61B 6/4014 20130101; G01R 33/4808 20130101; A61B 5/0035 20130101;
A61B 6/032 20130101; A61B 6/4417 20130101; A61B 5/0073 20130101;
A61B 6/4266 20130101; G06T 11/005 20130101; A61B 6/508 20130101;
A61B 6/466 20130101; A61B 5/055 20130101; A61B 5/0071 20130101;
A61B 5/0077 20130101 |
Class at
Publication: |
600/427 ;
600/476 |
International
Class: |
A61B 5/00 20060101
A61B005/00; G01R 33/48 20060101 G01R033/48; A61B 5/055 20060101
A61B005/055; A61B 6/03 20060101 A61B006/03; A61B 6/00 20060101
A61B006/00 |
Claims
1. A system, comprising: first imaging equipment for imaging an
object to produce a reconstructed image; and second imaging
equipment comprising a camera housed in a light-free housing and
configured to detect optical signals emitted from the object, the
second imaging equipment being further configured to: map optical
properties of the object to the reconstructed image, the map step
yielding mapped optical properties of the object and reconstructing
an optical source distribution of the object based at least on the
detected optical signals and the mapped optical properties.
2. The system of claim 1, wherein the camera is a cooled
back-thinned charge-coupled device (CCD) camera.
3. The system of claim 1, wherein the first imaging equipment is
tomographic X-ray imaging equipment.
4. The system of claim 1, wherein the second imaging equipment is
further configured to detect the optical signals emitted from the
object in three dimensions.
5. The system of claim 4, wherein the second imaging equipment is
further configured to detect substantially sequentially the optical
signals emitted from the object at multiple angles.
6. The system of claim 4, wherein the second imaging equipment is
further configured to detect sequentially the optical signals
emitted from the object at multiple angles of view.
7. The system of claim 1, wherein the cooled back-thinned CCD
camera is in communication with a control element configured to
control said camera.
8. The system of claim 7, wherein the control element is further
configured to control at least one imaging parameter of the cooled
back-thinned CCD camera, the at least one imaging parameter
comprising one or more of a focus, an exposure time, or an
aperture.
9. The system of claim 1, wherein the optical properties comprise
at least one of absorption coefficients, indices of refraction,
scattering coefficients, or scattering anisotropy.
10. The system of claim 1, wherein the optical source distribution
is produced using a radiative transfer equation or an approximation
to the radiative transfer equation.
11. A method, comprising: acquiring first imaging data from an
object to produce a reconstructed image of the object; detecting
optical signals emitted from the object; mapping optical properties
of the optical signals from the object to the reconstructed image
of the object; and reconstructing an optical source distribution of
the object based at least on the detected optical signals and the
mapped optical properties, wherein the optical source distribution
is produced using a radiative transfer equation or an approximation
to the radiative transfer equation.
12. The method of claim 11, wherein the detecting step comprises
collecting the optical signals at a plurality of locations arranged
on a surface surrounding the object.
13. The method of claim 11, wherein the detecting step comprises
detecting substantially simultaneously the optical signals emitted
from multiple angles of view.
14. The method of claim 11, wherein the detecting step comprises
detecting sequentially the optical signals emitted from multiple
angles of view.
15. The method of claim 11, wherein supplying data for mapping the
optical properties of the object to the reconstructed image of the
object comprises supplying data for estimating the scattering
properties and the optical absorption properties of the object.
16. An apparatus, comprising: means for acquiring first imaging
data from an object to produce a reconstructed image; means for
detecting optical signals emitted from the object; means for
mapping optical properties of optical signals from the object to
the reconstructed image of the object; and means for reconstructing
an optical source distribution of the object based at least on the
detected optical signals and the mapped optical properties.
17. The apparatus of claim 16, wherein the optical source
distribution is produced using a radiative transfer equation or an
approximation to the radiative transfer equation.
18. The apparatus of claim 16, wherein the means for detecting the
optical signals emitted from the object comprises means for
collecting the optical signals at a plurality of locations arranged
on a surface surrounding the object.
19. The apparatus of claim 16, further comprising means for
rotating the object about at least one axis.
20. The apparatus of claim 16, further comprising means for moving
the object among a location associated with the means for acquiring
first imaging data and a location associated with the means for
detecting the optical signals emitted from the object.
21. The system of claim 1, wherein the optical signals are induced
by laser.
22. The method of claim 11, wherein the optical signals are induced
by laser.
23. The apparatus of claim 16, wherein the optical signals are
induced by laser.
24. The system of claim 1, wherein the optical signals are induced
by a beam of electromagnetic waves.
25. The method of claim 11, wherein the optical signals are induced
by a beam of electromagnetic waves.
26. The apparatus of claim 16, wherein the optical signals are
induced by a beam of electromagnetic waves.
Description
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application is a continuation of U.S. patent
application Ser. No. 10/791,140 filed Mar. 2, 2004, which claims
priority from U.S. Provisional Application No. 60/453,177 filed
Mar. 10, 2003, each of which are hereby incorporated by reference
in their entirety.
BACKGROUND
[0002] This invention relates to multi-modality-based systems and
methods for detecting an optical property distribution, such as a
light-emitting source distribution, in multiple dimensions as well
as systems and methods for reconstructing such an image from the
detected signals from the distribution based on data from a
tomographic imaging modality, including but not limited to computed
tomography (CT) or micro-CT.
[0003] There are many "emission-detection" imaging techniques known
in the art, such as bioluminescent imaging. However, such current
imaging techniques are limited to the projective imaging mode or
external excitation of the internal light source through external
energy sources along selected paths. Therefore, three-dimensional
structures and localization of an internally derived light source,
such as one not reliant on external energy excitation, cannot be
resolved with high quantitative accuracy both in terms of spatial
location and localized activity.
[0004] Diffuse computed tomography (CT), another known imaging
technique, computes distributions of absorption and scattering
coefficients from scattered light through an object. Typically,
intensity-modulated light sources are used. It is well known that
diffuse CT will generally produce low image resolution,
particularly as background heterogeneity increases.
[0005] It would therefore be desirable to combine an optical
imaging technique, such as a light emission technique, specifically
bioluminescent imaging, with a scanning technique that allows the
evaluation of two and three dimensional structural information,
such as computed tomography scanning or magnetic resonance imaging,
to produce a reconstructed image having better image
resolution.
SUMMARY
[0006] The present invention is directed to multi-modal imaging
systems and methods that reconstruct images via fundamental and
synergistic utilization of multi-model data. According to an
exemplary embodiment, an image volume may be reconstructed in a
first tomographic modality, optical properties from a database may
be mapped to the image volume, and the image may then be
reconstructed tomographically in another modality, based on the
optical properties.
[0007] According to one embodiment, bioluminescent CT and
CT/micro-CT combinations may be used, but other system
configurations are possible. Some embodiments may include a
magnetic resonance imaging (MRI) scanner or micro-MRI scanner in
conjunction with a fluorescent tomographic scanner. The imaging
techniques and algorithms described herein are exemplary only, and
other methods of combining data from two or more tomographic
scanners may be used.
[0008] Some embodiments may be capable of various resolutions
depending on scanning times, possess extremely high photon
detection sensitivity for mapping gene expression, and/or embody
hardware and/or software technology for image reconstruction,
registration, and analysis. Some embodiments may have the advantage
of being configured to rapidly collect data with a higher
signal-to-noise ratio.
[0009] According to one embodiment, bioluminescent imaging may be
rendered in a two- or three-dimensional tomographic modality. In
embodiments directed to bioluminescence, emitted photons can be
collected from multiple three-dimensional directions with respect
to an animal marked by bioluminescent compounds including reporter
luciferases.
[0010] According to some embodiments, a CT or micro-CT scanner may
be integrated with a bioluminescent imaging system. The
bioluminescent imaging system may also be combined with other
imaging systems which provide information regarding the
distribution of tissue structures in vivo, in situ, or ex vivo.
[0011] In alternative embodiments, an object may be serially
scanned using each modality in turn. In still further embodiments,
the object may be transported between scanning modalities.
Optionally, one or more registration marks may be placed on the
object to coordinate positions between scanning modalities. The
surface of the object may also be optically reconstructed for the
registration purpose.
[0012] In some embodiments, information associated with x-ray CT
imaging and bioluminescent imaging may be used together to estimate
light scatter and/or other optical properties of tissue and thereby
reconstruct a three-dimensional emission image volume registered to
corresponding CT or micro-CT imaging of anatomical and pathological
structures. As non-limiting examples, the system may be used to
generate images of structures, such as bioluminescent sources,
lungs and various tumors.
[0013] According to some embodiments, intra-organ localization of
gene transcription activity may be performed with resolution
capable of differentiating, for instance, gene expression in the
central pulmonary airways (out to approximately the 5th-7th
generation) versus parenchymal activity. Also, localization of
parenchymal activity in terms of sub-lobar regions may be
performed. As a non-limiting example, small animal imaging, in
particular mouse imaging, may be performed. In other examples, the
systems and methods may be used for other biomedical applications
where bioluminescent signals are detectable. Some embodiments are
especially suited for small animal imaging at molecular levels. For
example, genetic activity in a particular organ system may be
imaged.
[0014] By integrating x-ray and optical imaging, better optical
tomography image quality can be achieved that would not be possible
with a stand-alone optical system. From a corresponding x-ray CT
image volume or image volume generated by other imaging energy
sources, knowledge of the underlying distribution of optical
scatters can be derived. This information is useful in
reconstruction of images from optical data. Specifically, emitting
source distributions may be directly solved for, obviating the need
for reconstruction of optical properties in three dimensions.
[0015] According to exemplary embodiments, the combined use of
x-ray CT and BLCT transforms the nonlinear optical CT problem into
an easier linear problem. Therefore, the reconstruction of image
data from a bioluminescent CT scanner may be significantly
improved.
[0016] One embodiment includes a system processor that supports the
desired functionality as described in detail below and a system
data store (SDS) that stores data associated with the needed
functionalities, such as image data and reconstruction. The system
processor may be in communication with the SDS via any suitable
communication channel(s).
[0017] The SDS may include multiple physical and/or logical data
stores for storing the various types of information used. Data
storage and retrieval functionality can be provided by either the
system processor or one or more data storage processors associated
with the SDS. The system processor may include one or more
processing elements that are adapted or programmed to support the
desired image storage, reconstruction and/or other
functionality.
[0018] Accordingly, one method of image reconstruction includes a
variety of steps that may, in certain embodiments, be executed by
the environment summarized above and more fully described below or
be stored as computer executable instructions in and/or on any
suitable combination of computer-readable media. The steps can
include but are not limited to performing tomographic
reconstruction of an image volume in one modality, mapping optical
properties to that volume from a database, and performing
tomographic reconstruction in another modality based on the mapped
optical properties.
[0019] Additional advantages of the invention will be set forth in
part in the description which follows, and in part will be obvious
from the description, or may be learned by practice of the
invention. It is to be understood that both the foregoing general
description and the following detailed description are exemplary
and explanatory only and are not restrictive of the invention as
claimed.
BRIEF DESCRIPTION OF THE DRAWINGS
[0020] The accompanying drawings, which are incorporated in and
constitute a part of this specification, illustrate embodiments of
the invention and together with the description, serve to explain
the principles of the invention.
[0021] FIG. 1 depicts an exemplary bioluminescent imaging device
(left panel) with an anatomic imaging device (micro CT scanner
shown in the right panel).
[0022] FIG. 2 depicts an exemplary single source bioluminescent CT
scanner. The rotating stage and light sensitive camera is shown on
the bottom shelf of the cart. The side of the light tight enclosure
has been removed for system visualization.
[0023] FIG. 3 depicts bioluminescence emitted from the lungs of a
mouse following exposure to an adenovirus which has delivered the
primary gene and reporter gene (producing luciferase) to the lungs.
The emitted light can be seen from multiple angles according to
exemplary embodiments. This is a precursor to being able to
reconstruct the 3D distribution of the light source(s).
[0024] FIG. 4 depicts an exemplary micro-CT image of a lung showing
structural components of the mouse thorax with resolution down to
the alveolar level. This sort of anatomic image serves to provide
the knowledge of the distribution of light scatterers.
DETAILED DESCRIPTION
[0025] One or more exemplary embodiments are now described in
detail hereinbelow and in the attachments hereto. Referring to the
drawings, like numbers indicate like parts throughout the views. As
used in the description herein and attachments hereto, the meaning
of "a," "an," and "the" includes plural reference unless the
context clearly dictates otherwise. Also, as used in the
description herein and attachments hereto, the meaning of "in"
includes "in" and "on" unless the context clearly dictates
otherwise. Finally, as used in the description herein and
attachments hereto, the meanings of "and" and "or" include both the
conjunctive and disjunctive and may be used interchangeably unless
the context clearly dictates otherwise.
[0026] Ranges may be expressed herein as from "about" one
particular value, and/or to "about" another particular value. When
such a range is expressed, another embodiment includes from the one
particular value and/or to the other particular value. Similarly,
when values are expressed as approximations, by use of the
antecedent "about," it will be understood that the particular value
forms another embodiment. It will be further understood that the
endpoints of each of the ranges are significant both in relation to
the other endpoint, and independently of the other endpoint.
[0027] The present invention relates to systems and methods for
detecting a light-emitting source distribution as well as systems
and methods for reconstructing an image from the detected light
signals and tomographic images obtained from one or more other
modalities, such as an image volume from CT or micro-CT. Some
embodiments may include one or more cameras arranged, e.g.,
symmetrically, on a spherical surface to detect a light emitting
source distribution in three dimensions. Alternative embodiments
may include asymmetrical camera arrangements and/or other
three-dimensional surface arrangements. In some embodiments, other
optical mechanisms can be used to intercept and direct signals to
the cameras including, but not limited to, mirror and/or fiber
systems.
[0028] Some further embodiments may detect and record
bioluminescent emissions and/or fluorescent emissions. This image
data, along with associated x-ray CT images of the same object, can
be used to reconstruct a three-dimensional emission image volume
and register the bioluminescent CT image to a corresponding x-ray
CT or micro-CT image volume of anatomical and pathological
structures. In some such embodiments, the bioluminescent (or
fluorescent) reconstruction process can be enhanced through the use
of knowledge gained from x-ray CT or other anatomic information
gathered by use of other imaging devices including, but not limited
to, MRI or ultrasound. As a non-limiting example, emitted photons
can be collected from multiple directions in three dimensions with
respect to a living animal or any other light emitting structure of
interest marked by bioluminescent reporter luciferases or
fluorescent sources. In some embodiments, a lung and/or various
tumors may be imaged.
[0029] According to exemplary embodiments, optical properties of an
object are presumed to be already known, and the photon-emitting
source distribution may be computed based on these known optical
properties. Therefore, the imaging models for the systems and
methods according to exemplary embodiments are approximately
linear, while that for the conventional techniques, such as diffuse
CT, are nonlinear and correspondingly more difficult to solve.
[0030] By combining a system for detecting light emission from
multiple angles of view simultaneously or sequentially with an
imaging modality which allows the evaluation of two and three
dimensional structural information, such as micro x-ray CT, the
anatomic and/or structural details gained from the micro x-ray CT
can be used to estimate the distribution of light scattering
structures for purposes of directing the computed tomographic
calculations required to create BLCT cross-sectional or volumetric
images. Such a system may enable, as non-limiting examples, both
the calculation of the computed tomograms of chemo-luminescence and
the linking of the computed tomograms of chemo-luminescence to the
highly detailed anatomic image sets derived from the x-ray CT
imaging. In some embodiments, the tomographic reconstruction of
bioluminescence can provide important added detail regarding
regional location of reporter gene activity. By knowing the
location of reporter gene activity and having micro-resolution
images of anatomy, a user can follow the link between gene
activation and pathologic processes.
Typical Storage and Processing Architecture
[0031] In one exemplary embodiment, the imaging and reconstruction
system includes a system processor potentially including multiple
processing elements. The term processing element may refer to (1) a
process running on a particular piece, or across particular pieces,
of processing hardware, (2) a particular piece of processing
hardware, or either (1) or (2) as the context allows. Each
processing element can be supported via a standard general purpose
processor such as an Intel-compatible processor platforms
preferably using at least one CELERON, PENTIUM, XEON, ITANIUM
(Intel Corp., Santa Clara, Calif.) class processor, alternative
processors such as MIPS (MIPS Technologies, Mountain View, Calif.)
or UltraSPARC (Sun Microsystems, Palo Alto, Calif.) could be used
in other embodiments. The system processor, or the one or more
processing elements thereof, can include one or more field
programmable gate arrays (FPGAs), programmable digital signal
processors (DSPs) and/or application specific integrated circuits
(ASICs) configured to perform at least a portion of the
functionality according to the present invention. In other
embodiments, an embedded microprocessor can be used such as, but
not limited to, an ARM (ARM, Carlsbad, Calif.) processor core.
[0032] In some embodiments, the system processor can include a
combination of general purpose processors, ASICs, DSPs and/or
FPGAs. In some embodiments, the systems and methods of the present
invention, as described above, can be distributed across multiple
processing elements. In some such embodiments, aspects of the
functionality or portions thereof may be executed in series or in
parallel; particular functionality or portions thereof executed a
multiplicity of times may also occur in series or parallel.
[0033] In a system processor including at least one general purpose
processor, the general purpose processor typically runs an
appropriate operating system such as WINDOWS/NT, WINDOWS 2000 or
WINDOWS/XP (Microsoft, Redmond, Wash.), IRIX (Silicon Graphics,
Mountain View, Calif.), SOLARIS (Sun Microsystems, Palo Alto,
Calif.), or LINUX (or other UNIX variant). In one embodiment, the
Windows 2000 operating system is used.
[0034] The SDS may include a variety of primary and secondary
storage elements. In one embodiment, the SDS can include random
access memory (RAM) as part of the primary storage; the amount of
RAM might range from 512 MB to 4 GB in some embodiments. The
primary storage can, in some embodiments, include other forms of
memory such as cache memory, registers, non-volatile memory (e.g.,
FLASH, ROM, EPROM, etc.), etc.
[0035] The SDS can also include secondary storage including single,
multiple and/or varied servers and storage elements. For example,
the SDS can use internal storage devices connected to the system
processor. In embodiments where a single processing element
supports all of the system functionality, a local hard disk drive
can serve as the secondary storage of the SDS, and a disk operating
system executing on such a single processing element can act as a
data server receiving and servicing data requests. A system bus can
serve as the communication channel between the system processor and
the SDS (typically, at least RAM and the hard disk drive).
[0036] It will be understood by those skilled in the art that the
different information used in the imaging and image reconstruction
processes and systems according to the present invention can be
logically or physically segregated within a single device serving
as secondary storage for the SDS; multiple related data stores
accessible through a unified management system, which together
serve as the SDS; or multiple independent data stores individually
accessible through disparate management systems, which may in some
embodiments be collectively viewed as the SDS. The various storage
elements that comprise the physical architecture of the SDS may be
centrally located or distributed across a variety of diverse
locations.
[0037] The architecture of the secondary storage of the system data
store may vary significantly in different embodiments. In several
embodiments, database(s) are used to store and manipulate the data;
in some such embodiments, one or more relational database
management systems, such as DB2 (IBM, White Plains, N.Y.), SQL
Server (Microsoft. Redmond, Wash.), ACCESS (Microsoft, Redmond,
Wash.), ORACLE (Oracle Corp., Redwood Shores, Calif.), Ingres
(Computer Associates, Islandia, N.Y.), MySQL (MySQL AB, Sweden) or
Adaptive Server Enterprise (Sybase Inc., Emeryville, Calif.), may
be used in connection with a variety of storage devices/file
servers that may include one or more standard magnetic and/or
optical disk drives using any appropriate interface including,
without limitation, ATA, IDE and SCSI. In some embodiments, a tape
library such as available from Exabyte Corporation (Boulder,
Colo.), a storage attached network (SAN) solution such as available
from EMC, Inc. (Hopkinton, Mass.), a network attached storage (NAS)
solution such as available from Network Appliances (Sunnyvale,
Calif.), or combinations thereof may be used. In other embodiments,
the data store may use database systems with other architectures
such as object-oriented, spatial, object-relational or
hierarchical.
[0038] Instead of, or in addition to, those organization approaches
discussed above, certain embodiments may use other storage
implementations such as hash tables or flat files or combinations
of such architectures. Such alternative approaches may use data
servers other than database management systems such as a hash table
look-up server, procedure and/or process and/or a flat file
retrieval server, procedure and/or process. Further, the SDS may
use a combination of any of such approaches in organizing its
secondary storage architecture.
[0039] The SDS communicates with the system processor by one or
more communication channels. Multiple channels can be involved in
some embodiments for supporting communication between processing
elements of the system processor and portions of the SDS. Such
channels can include without limitation computer network, direct
dial-up connection, dedicated connection, direct or indirect
connection such as via a bus connection, parallel or serial
connection, USB connection, null modem connection or wireless
connection utilizing an appropriate communication protocol such as
BLUETOOTH, IRDA, 802.11b or other suitable channel as would be
known to those skilled in the art.
[0040] All forms of data, including raw, intermediate, and computed
can be stored on one or more SDS either temporarily or permanently.
In particular, the SDS can store, without limitation, image data,
including volumetric image data, reconstruction intermediate data,
final reconstructed imaging data, imaging parameters, and
reconstruction parameters. Further, the SDS may, in some
embodiments, store instructions for performing the various imaging
and reconstruction tasks, or portions of such tasks.
Light Sensitive Cameras
[0041] In one embodiment, ten CCD cameras can be arranged at the
center of each identical face of a dodecahedron, except for the two
facing the front and back ends of an object to be imaged. Each of
the 10 cameras can point to the iso-center where the object can be
fixed on a holder. The imaging geometry can be implemented by a
structure holding each camera in its fixed position. Data from the
cameras can be transmitted to one or more processing elements for
further processing and image reconstruction. A light-free housing
can be used to house the imaging cameras. Once the frame of the
imaging device is arranged, a camera can be mounted at any spot of
the 12 nominal positions on the dodecahedron. One or more cameras
can be geometrically and photographically calibrated with reference
phantoms. An optical surface scanner can be combined with the
imaging frame for the registration purpose.
[0042] One skilled in the art will recognize that other
arrangements of cameras are possible, including geometrically
symmetrical and asymmetrical configurations, with or without
appropriate optical paths such as obtained through use of mirrors
or fiberoptic relay paths. In some embodiments, one or more cameras
can be rotated around an object of interest. Alternatively, or in
combination, the subject of the imaging can be rotated on one or
more axis. As a non-limiting example, such embodiments can be used
in cases where light emission is unstable. In this case, dynamic
bioluminescent and/or fluorescent tomographic imaging would be
feasible.
[0043] In one embodiment, one or more cooled back-thinned
integrating CCD cameras can be used for imaging. The camera package
can include a 2.2 L or other appropriately sized end-on liquid
nitrogen dewar for cooling. Alternatively, an omni-directional
dewar can be used to allow cameras to be mounted in any orientation
while keeping the dewar right-side up. In some embodiments, the
imagers can be sensitive to one or more bioluminescent sources of
different spectral characteristics. Other types of light sensitive
cameras can also be used. Analog films can be used with appropriate
manipulations.
[0044] A living organism, or other structure of interest, can be
scanned using a multi-detector spiral CT, another appropriate
method of imaging known to one skilled in the art, or a micro x-ray
CT scanner. From this imaging, a distribution of optical properties
of the object can be derived to guide associated bioluminescent
and/or fluorescent tomographic imaging.
Camera Control
[0045] According to exemplary embodiments, one or more camera
control elements may be used. A camera control element can include
one or more processing elements and can be in communication with
the SDS. The imaging cameras of the present invention can be in
communication with the one or more camera control elements. Camera
control elements can perform digitization of output from cameras
and other processing as appropriate. Relevant imaging parameters
can be controlled by the camera control elements. As non-limiting
examples, imaging parameters such as focus, exposure time,
aperture, can be configured. Additional parameters known to one
skilled in the art can also be configured as appropriate.
[0046] In some embodiments, all cameras can be controlled by a
single controller element. In other embodiments, a single
controller element may be used to control multiple cameras. In such
an embodiment, cameras may be arbitrarily grouped into arrays and
each array can be controlled by a single controller element. Each
camera acquisition chain can then operate independently. Still
further embodiments can include a master controller element to
provide control and synchronization for an entire camera array. In
one embodiment, one camera is controlled by a single controller
element. One skilled in the art will recognize that other
configurations of cameras and controller elements are possible.
[0047] Some embodiments can include one or more hierarchies of
control elements and/or processing elements. Different levels of
hierarchy can perform the same or different functions. In one
embodiment, images from low-level camera control elements are
passed to higher level processing elements and/or control elements
for additional processing and/or image reconstruction, as further
described below. Control elements and processing elements can be
communicatively coupled via any suitable communication means
including computer network, wired or wireless direct link, bus
connection and as further described below.
[0048] In one embodiment, individual cameras can be controlled with
an external camera control element in communication with a PCI
controller card in communication with one or more processing
elements. The PCI controller card and the camera control element
can be communicatively coupled via an RS-422 link or other suitable
serial or parallel connection. The external camera control element
and the camera can be communicatively coupled via a parallel
interface. In one such embodiment, cameras output analog signals
which are digitized by one or more external camera control
elements. To minimize noise, the length of the link between the
camera and the controller box can be minimized.
[0049] In one embodiment, the light-emitting source data
acquisition process can include one or more of the following steps:
(1) reset and/or initialize cameras; (2) execute a programmable,
configurable, or manual shutter open on one or more cameras; (3)
execute a programmable, configurable, or manual shutter close on
one or more cameras; (4) transfer image data to one or more camera
control elements, processing element, or SDS; and (5) store the
images in the SDS. Additional embodiments can have shutter times
configured to occur simultaneously across multiple cameras and/or
automatically after a predetermined time delay.
Image Reconstruction Using an Iterative Method or Other Methods
[0050] Given the ill-posed nature of the imaging and sampling
geometry, an iterative image reconstruction approach may be used
utilizing prior knowledge on the distribution to be reconstructed.
The iterative approach can be used in the case of incomplete and/or
noisy data. Also, the iterative approach easily accommodates prior
knowledge and imaging physics.
[0051] An interface from one or more camera control elements and/or
processing elements to one or more reconstruction engines can be
provided. The systems of the present invention can acquire optical
properties of the object being imaged and then compute the
light-emitting source distribution based on the optical properties.
Therefore, the imaging model is approximately linear. In one
embodiment, x-ray CT data is used to regularize the BLCT
reconstruction problem and transform it from a nonlinear one to
linear one and thereby greatly simplify it.
[0052] Even with attenuation and scattering taken into account
based on a CT or micro-CT image volume, a discrete BLCT imaging
model can still be linearly expressed as Ax=b, where the observed
data b=(b.sup.1, . . . , b.sup.M).epsilon.R.sup.M, original
emitting source distribution x=(x.sub.1, . . . ,
x.sub.M).epsilon.R.sup.N, and a known non-zero M.times.N matrix
A=(A.sub.ij). The coefficients of the matrix A depend on the
anatomical structures and their optical properties according to the
classic Radiative Transfer Equation (using the Monte Carlo method)
or the well-known diffusion approximation or another appropriate
method. The systems and methods according to exemplary embodiments
can reconstruct the image x from the data b.
[0053] A generalized BLCT algorithm according to one embodiment can
include one or more of the following steps: (1) reconstruction and
segmentation of an x-ray CT image volume, (2) association of
optical properties to each segmented region in the x-ray CT volume
based on a library of optical properties, (3) determination of
coefficients of the forward imaging matrix A=(A.sub.ij) based,
e.g., on Monte Carlo simulations, (4) reconstruction of the
emitting source distribution x by inverting the matrix A, subject
to the constraints imposed by the segmented anatomical structures,
their properties, and known features of the underlying source
distribution (such as the homogeneity or parametric form of the
source distribution, the shape or intensity of the source).
According to exemplary embodiments, bioluminescent emissions, and
well as other light-emitting source distributions, such as
fluorescent source distributions, may be detected and reconstructed
in this way or another alternative way.
[0054] As non-limiting examples, the optical properties of step two
can include absorption coefficients, scattering coefficients,
scattering anisotropy, indices of refraction, and other appropriate
parameters known to one skilled in the all. Monte Carlo simulations
can be used to predict bioluminescent signals and construct the
matrix A based on the CT/micro-CT image volume of the object. Other
methods, such as finite element methods and meshfree methods, may
be also used for this purpose. After image segmentation, optical
properties can be assigned to each segment based on a library of
optical properties.
[0055] In one embodiment, both the ordered-subset expectation
maximization (OS-EM) and the ordered-subset version of the
simultaneous algebraic reconstruction technique (OS-SART) schemes
for BLCT can be implemented. A roughness penalty method for BLCT or
other method known to one skilled in the art can also be used.
[0056] Although an iterative method may be most suitable to the
image reconstruction task in one embodiment, other image
reconstruction methods can be used. Even further, the iterative
procedure described above is only an example, and should not be
interpreted as a limiting description.
[0057] As far as image reconstruction methods are concerned, it is
emphasized that there are multiple options or possibilities. In
addition to an iterative reconstruction strategy as described
above, numerical solutions to the Radiative Transfer Equation or
its approximation, such as the diffusion equation, can be useful as
well. A fast analytic method would be very useful in practice. In
one embodiment, an analytic approach known as the Kirchhoff
approximation may be adapted for bioluminescent tomography of
diffuse media with an embedded source distribution. Other numerical
methods, such as finite element methods and/or meshfree methods,
are also feasible for the same purpose.
CT/Micro-CT Scanner
[0058] Any state-of-the-art micro-CT scanner can be used according
to exemplary embodiments. In some embodiments, the ImTek MicroCAT
II described, e.g., at
http://www.imtekinc.com/html/microcat_ii_specifications.html, or
the SkyScan-1076 in-vivo micro-CT system described, e.g., at
http://www.skyscan.be/next/spec.sub.--1076.htm, can be used.
[0059] In other embodiments, the data acquisition system can
include one or more of the following items: a dedicated embedded
data acquisition and control computer, two 130 kVp ultra-high
resolution .mu.focus X-ray systems, two 100/50 mm dual-field image
intensifiers, and two 2048.times.2048 CCD cameras. The scanner can
include one or more processing elements in communication with the
SDS, a multi-axis precision scanner and specimen manipulator with
linear servo drives, remotely configurable motorized
source-detector geometries, a signal and power slip ring for
continuous rotation, and a means to move data between acquisition
and processing. The slip ring can have two independent capacitively
coupled data transmission channels with full-duplex fibre channel
interfaces. The one or more processing elements, the slip ring data
channels and the SDS can be communicatively coupled. In one
embodiment, they can be connected via one or more fiber optic
cables.
[0060] One embodiment may be built on an optical grade table for
vibration isolation and precision alignment. An imaging chain of
source arrays, detector arrays, and accessories, alone or in
combination, can be mounted on a rotating plate which is in turn
supported by an open bearing and rigid stand. The axis of rotation
can set to any appropriate angle including vertical and horizontal.
The geometry of each imaging chain can be individually configured
to suit a wide variety of operating modes. Each x-ray tube and
image intensifier can be moved radially, while each image
intensifier can also be moved laterally. The object can rest
horizontally in a holder mounted to a linear axis with a certain
amount of axial travel room for slice positioning. One exemplary
embodiment is capable of achieving spatial resolution of 100 lp/mm
for excised samples, and temporal resolution of 1.8 seconds for
objects up to 120 mm in diameter. The system can be configured to
allow a wide range of intermediate combinations of scan time and
spatial resolution.
System Integration
[0061] The light-emitting source distribution CT device and the
anatomic imaging scanner, such as a micro x-ray CT scanner, can be
electronically and mechanically integrated but need not be in all
embodiments. In one embodiment, the hardware structures of the two
imaging units can share a table and/or a holder attached to a
table.
[0062] This embodiment can allow the translation of an object for
x-ray CT scanning to be extended into the light-emitting CT device
in a precise and/or repeatable fashion. Some embodiments may be
configured to optimize and integrate software packages for Monte
Carlo simulation (another kind of simulation, such as that based on
finite element computation), CT and/or micro-CT data preprocessing
and reconstruction, BLCT reconstruction, image visualization and
analysis. A user interface to perform and/or to configure such
functions can also be provided in some embodiments; in some such
embodiments, the user interface can further allow viewing of
results and may allow control of parameters with respect to such
viewing. Any software capable of performing such functions can be
implemented on one or more processing elements.
Exemplary Applications
[0063] The following applications are intended as illustrative
examples only and are not limiting of the invention. According to
exemplary embodiments, advanced imaging, such as lung imaging, is
enabled in that the structural and function information can be
obtained concurrently at the molecular level, and can be evaluated
on a regional, sub-lobar basis. This combination allows
simultaneous examination of gene expression and anatomic structures
and improves understanding of the human lungs.
[0064] Exemplary embodiments may be used in gene therapy imaging,
to probe the distribution of the administered gene, reporter genes,
such as those producing luciferase, can be included in the
transfecting virus. These genes cause the emission of light,
enabling the functional gene to be identified within the target
tissue.
[0065] Exemplary embodiments may also be useful in evaluating
transgene expression in the lung; gene transfer vectors; gene
transfer to the respiratory epithelium of mice; in vivo
bioluminescence imaging; understanding the site of transgene
expression in the lung; human lung lobe imaging and sheep-based
emphysema model evaluation; understanding the site of gene therapy,
and its consequences; and understanding the pathophysiology of
airway vs. alveolar infection.
[0066] The embodiments described above are given as illustrative
examples only. It will be readily appreciated by those skilled in
the art that many deviations and other applications may be made
from the specific embodiments disclosed in this specification
without departing from the scope of the invention.
* * * * *
References