Mr. Grable is the CEO and director of Research and
Development, Dr. Gkanatsios is Medical Physicist, and Dr.
Ponder is the Advanced Development Manager with Imaging
Diagnostic Systems, Inc., Plantation, FL.
The field of biomedical optics, the use of light in medicine,
has seen rapid growth over the last decade. The development of
non-invasive medical optical imaging (MOI) modalities using
harmless near infrared (NIR) light is a major goal of biomedical
optics research. Arguably, the most interesting application of MOI
is breast imaging, with the potential to provide a safer, and
possibly more effective, alternative to traditional x-ray
In 1929, Max Cutler reported the ability to differentiate
between normal and pathological breast tissue by eye using an
electric lamp to transilluminate the breast in a darkened room.
Over the years, researchers improved upon this technique, known as
diaphanography, by using more sensitive optical detectors and NIR
light sources that have greater transmission through the breast.
Typically, diaphanography images showed certain cancerous tumors as
dark regions, thought to be caused by greater attenuation of NIR
light by blood in the tumor-associated hypervascularisation.
However, the highly scattering optical properties of breast tissues
severely blurred the transmission images obtained with
diaphanography. The limited spatial resolution, around 2 cm or
worse, contributed to low sensitivity and specificity results
during clinical trials of diaphanography in the 1980s preventing
its acceptance as a clinically viable modality.
Technological advances in recent years, specifically pulsed
lasers and ultra-fast detectors, have revived interest in MOI. The
ability to illuminate the breast with picosecond pulses of NIR
laser light and measure the temporal distribution of transmitted
photons, known as the temporal point spread function (TPSF),
enables investigation of time-resolved approaches to MOI. In
contrast, diaphanography used a continuous wave (CW) light source
and all the transmitted photons through the breast. Phantom studies
have indicated that measuring the TPSF and using only the photons
arriving earliest at a detector (a technique known as time-gating)
can improve the image spatial resolution to about 1 cm. However,
the poor signal-to-noise ratio obtained by measuring only the
earliest photons ultimately limits the benefits of time-gating.
Nevertheless, phantom studies have demonstrated that by fitting an
analytic model based on diffusion theory to the TPSF and using the
model's predictions for early photons the image spatial resolution
of transmission images could be improved to about 5 mm.
An alternative to transmission images of the breast is to
acquire optical images in a similar fashion to x-ray computed
tomography (CT). Generally, this approach uses a modified
back-projection algorithm that is analogous to x-ray CT, but
incorporates the physics of NIR diffusion in the breast.
Back-projected slices yield the spatial variation in attenuation of
the NIR light within the breast. A more sophisticated approach to
reconstruct slice images uses a complex iterative inversion
technique to predict TPSFs, or some characteristic of them, via a
finite-element forward model based on diffusion theory.
This approach is theoretically more sound and enables the
attenuation of NIR light to be de-coupled into an absorption image
and a scattering image of the breast. It is anticipated this extra
information will significantly help diagnosis.
Several universities and a growing number of companies are
actively pursuing medical optical imaging with time-resolved
methods. Some have chosen to pursue similar ideas in the frequency
domain, which greatly reduces the complexity and expense of the
At present, however, the frequency domain systems acquire less
information content than time-resolved systems
Computer Tomography Laser Mammography
Since 1994, Imaging Diagnostic Systems Inc. (IDSI, Plantation,
FL) has been developing a computed tomography laser mammography
) system to serve as an adjunctive modality to x-ray mammography.
The CTLM system operates as a tomographic scanner to generate slice
images of the breast using non-ionizing NIR light and without
applying any breast compression. The patient lies in a prone
position with one breast pendent within the scanning chamber
(figure 1). A bank of NIR-sensitive detectors, mounted around a
horizontally rotating gantry, nearly encircles the breast without
touching it. The breast is illuminated in the same horizontal plane
mid-way between the first and last detectors by a pencil beam of
NIR light from a laser source on the gantry (figure 2). A complete
rotation of the gantry moves the pencil beam and bank of detectors
around the breast. During rotation, the detectors measure the light
transmitted through the breast from the pencil beam.
Simultaneously, CCD cameras on the gantry view the pencil beam on
the breast surface in order to measure the boundary shape of the
breast. Once rotation is completed, the gantry can be moved
vertically to another horizontal plane (slice) of the breast.
During a typical scan, the CTLM system starts at the chest wall and
acquires successive slices as the gantry is lowered down the
breast. The acquired data is fed to an image reconstruction
As mentioned previously, there are two main approaches to
reconstructing slice images of the breast from optical CT data.
Both a modified back-projection algorithm and an iterative
inversion algorithm are being evaluated at IDSI. The reconstructed
slice images can be displayed either volumetrically or as a series
of coronal, sagittal, and axial profiles.
Throughout its continuing development, the CTLM system has
existed as a variety of prototypes which all generally conform to
the description outlined above. Both CW and time-resolved CTLM
systems are in development; currently, the CW CTLM system is being
evaluated in a clinical environment.
Phantoms with optical properties similar to breast tissue have
been manufactured to help the development of the CTLM system. One
of these phantoms is a breast-shaped epoxy-based shell with breast
optical properties. The shell can be filled with a breast-like
scattering solution and inclusions can be added to simulate tumors.
For one experiment, the shell was filled with breast-like
scattering solution and a small cylindrical inclusion (1 cm
diameter, 1 cm height) was suspended inside it. The inclusion had
the same transport scattering coefficient as the surrounding medium
and 10 times greater absorption coefficient. The phantom was
scanned using the CW CTLM system and slices were reconstructed with
the modified back-projection algorithm. Figure 3 shows a volumetric
image of the reconstructed slices of the phantom where the
inclusion is clearly identified within the shell.
Phantom experiments have been good predictors of in vivo CTLM
performance. Figure 4 shows results of a unilateral CTLM multislice
scan of a normal volunteer with fatty breasts. Vascularisation and
a well-localized area of dense tissue are visible.
A further avenue of development is the possibility of
incorporating optical contrast agents to improve diagnosis.
Fluorophores that absorb NIR light at one wavelength and fluoresce
at another could be used as markers when injected into a patient.
This technique could involve either specific targeting of the
fluorophore to a certain type of tumor, or a non-specific approach
relying on greater uptake of the fluorophore by the tumor due to
hypervascularisation. Several major pharmaceutical companies are
now expressing interest in developing optical contrast agents.
These could be used in conjunction with a modified CTLM system,
which has already demonstrated localization of a fluorescent
inclusion within a breast-like phantom.
The results so far are highly encouraging and indicate the
clinical potential of optical mammography. As expected, the spatial
resolution shown in Figures 3 and 4 is poor since they were
acquired with the CW CTLM system. However, it is anticipated that
the spatial resolution will be greatly improved with the
time-resolved CTLM system. Furthermore, the employment of optical
contrast agents to aid diagnosis is an exciting proposition for the
future. Ultimately, the outcome of clinical trials will determine
the viability of the CTLM system in the breast-imaging market.
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