In the search for improved imaging modalities for detection and diagnosis of breast cancer, a high negative prediction value is also important. Photoacoustic (optoacoustic) imaging is a relatively new technique that has high potential for visualizing breast malignancies, but little is known about the photoacoustic appearance of benign lesions. In this work, we investigate the visibility of benign breast cysts in forward-mode photoacoustic mammography using 1064-nm light, as currently applied in the Twente photoacoustic mammoscope. Results from (Monte Carlo and k-wave) simulations and phantom measurements were used to interpret results from patient measurements. There was a strong agreement among the results from simulations, phantom, and patient measurements. Depending on the absorption contrast between cyst and breast tissue, cysts were visible as either one or two confined high-contrast areas representing the front and the back of the cyst, respectively. This edge enhancement is most likely the consequence of the local sudden change in the absorbed energy density and Grüneisen coefficients. Although the current forward-mode single-wavelength photoacoustic mammoscope cannot always unambiguously discriminate cysts from malignancies, this study reveals specific features of cysts compared to malignancies, which can be exploited for discrimination of the two abnormalities in future modifications of the imager.
Breast cancer is the most common form of cancer and the leading cause of cancer death among females. Early diagnosis improves the survival chances for the disease and that is why there is an ongoing search for improved methods for visualizing breast cancer. One of the hallmarks of breast cancer is the increase in tumor vascularization that is associated with angiogenesis: a crucial factor for survival of malignancies. Photoacoustic imaging can visualize the malignancyassociated increased hemoglobin concentration with optical contrast and ultrasound resolution, without the use of ionizing radiation or contrast agents and is therefore theoretically an ideal method for breast imaging. Previous clinical studies using the Twente Photoacoustic Mammoscope (PAM), which works in forward mode using a single wavelength (1064 nm), showed that malignancies can indeed be identified in the photoacoustic imaging volume as high contrast areas. However, the specific appearance of the malignancies led to questions about the contrast mechanism in relation to tumor vascularization. In this study, the photoacoustic lesion appearance obtained with an updated version of PAM is compared with the lesion appearance on Magnetic Resonance Imaging (MRI), both in general (19 patients) and on an individual basis (7 patients). Further, in 3 patients an extended histopathology protocol is being performed in which malignancies are stained for vascularity using an endothelial antibody: CD31. The correspondence between PAM and MRI and between PAM and histopathology makes it likely that the high photoacoustic contrast at 1064 nm is indeed largely the consequence of the increased tumor vascularization.
Elastic scattering of light in tissue offers a natural biologic contrast that can be used to classify tissue for diagnostic purposes. For a single fiber reflectance spectroscopy setup, which uses a single multimode optical fiber with diameter dfib for both illumination and detection, our group has previously reported a relationship between the single fiber reflectance (SFR) signal and the dimensionless scattering (μ′sdfib). Based on this relationship, the multi-diameter single fiber reflectance method (MDSFR), was developed. This method allows the extraction of μ′S and a phase function dependent parameter γ=(1-g2) / (1-g1) from tissue by taking multiple SFR measurements with different fiber diameters. Limitations and the sensitivity of the MDSFR method have been discussed previously based on an in silico analysis and the feasibility of the method has been proven experimentally during measurements in scattering phantoms containing polystyrene spheres. In the current study we will present data from an in-vivo clinical study utilizing MDSFR to determine tissue scattering properties of healthy and malignant breast tissue, on patients undergoing biopsy of a suspicious lesion found during mammographic breast imaging. Here MDSFR measurements are performed with a custom made disposable probe, incorporating two fiber diameters (0.4 and 0.8 mm), which is inserted through the biopsy needle before the biopsy is taken, allowing in vivo spectroscopic measurements of tumor center and healthy tissue.
In photoacoustic imaging, upon short laser pulse irradiation, absorbers generate N-shaped pulses which can be detected
by ultrasound transducers. Radio frequency signals from different spatial locations are then reconstructed taking into
account the ultrasound transducer angular response. Usually, the directivity is part of the "a priori" characterization of the
transducer and it is assumed to be constant in the reconstruction algorithm.
This approach is valid in both transmission and reflection ultrasound imaging, where any echo resembles the transducer
frequency response. Center frequency and bandwidth of any echo are almost the same, and the ultrasound transducer
collect signals with the same "fixed" acceptance angle. In photoacoustics, instead, absorbers generate echoes whose time
duration is proportional to the absorber size. Large absorbers generate low frequency echoes, whereas small absorber
echoes are centered at higher frequencies. Thus for different absorber sizes, different pulse frequencies are obtained and
different directivities need to be applied.
For this purpose once a radio-frequency signal is aquired, it is pre-processed with a sliding window: every segment is
Fourier transformed to extract the central frequency. Then, a proper directivity can be estimated for each segment.
Finally signals can be reconstructed via a backprojection algorithm, according to the system's geometry. Echoes are
backprojected over spheres with the angular extension being adapted to the frequency content of the photoacoustic
sources.
Simulation and experimental validation of this approach are discussed showing promising results in terms of image
contrast and resolution.
Current imaging modalities are often not able to detect early stages of breast cancer with high imaging contrast.
Visualizing malignancy-associated increased hemoglobin concentrations might improve breast cancer diagnosis.
Photoacoustic imaging can visualize hemoglobin in tissue with optical contrast and ultrasound resolution, which makes it
potentially ideal for breast imaging. The Twente Photoacoustic Mammoscope (PAM) has been designed specifically for
this purpose. Based on a successful pilot study in 2007, a large clinical study using PAM has been started in December
2010. PAM uses a pulsed Q-switched Nd:YAG laser at 1064 nm to illuminate a region of interest on the breast.
Photoacoustic signals are detected with a 1MHz, unfocused ultrasound detector array. Three dimensional data are
reconstructed using an acoustic backprojection algorithm. Those reconstructed images are compared with conventional
imaging and histopathology. In the first phase of the study, the goal was to optimize the visualization of malignancies.
We performed sixteen technically acceptable measurements on confined breast malignancies. In the reconstructed
volumes of all malignancies, a confined high contrast region could be identified at the expected lesion depth. After ten
successful measurements, the illumination area was increased and the fluence was substantially decreased. This caused a
further significant increase in PAM lesion contrast.
A popular phantom in photoacoustic imaging is poly(vinyl alcohol) (PVA) hydrogel fabricated by freezing and thawing (F-T) aqueous solutions of PVA. The material possesses acoustic and optical properties similar to those of tissue. Earlier work characterized PVA gels in small test specimens where temperature distributions during F-T are relatively homogeneous. In this work, in breast-sized samples we observed substantial temperature differences between the shallow regions and the interior during the F-T procedure. We investigated whether spatial variations were also present in the acoustic and optical properties. The speed of sound, acoustic attenuation, and optical reduced scattering coefficients were measured on specimens sampled at various locations in a large phantom. In general, the properties matched values quoted for breast tissue. But while acoustic properties were relatively homogeneous, the reduced scattering was substantially different at the surface compared with the interior. We correlated these variations with gel microstructure inspected using scanning electron microscopy. Interestingly, the phantom's reduced scattering spatial distribution matches the optical properties of the standard two-layer breast model used in x ray dosimetry. We conclude that large PVA samples prepared using the standard recipe make excellent breast tissue phantoms.
A large surface area transducer is preferable to be used to detect extremely weak photoacoustic signals in
mammography due to its high sensitivity. The lateral resolution is limited by the small acceptance angle of such
a transducer. We introduce an excellent material for an acoustic lens used to enlarge the transducer's acceptance
angle. Our acoustic characterizations showed that this material has tissue-like acoustic impedance, large speed
of sound and low acoustic attenuation. These acoustic properties ensures an excellent acoustic lens material.
We further investigated the acoustic irradiation pattern of a 1 MHz, 5 mm x 5 mm single element transducer.
Transducer irradiation pattern with and without acoustic lens made from our proposed material and common
used lens material are simulated using the Field II program and also the k-wave package. Good agreement has
been achieved comparing the simulation results from two different methods. Both simulations show that the
proposed material not only enlarged the acceptance angle of the transducer but also minimized the signal loss
compared to the common used lens material. We conclude that the proposed material can be used as an excellent
acoustic lens for photoacoustic tomography.
Worldwide, yearly about 450,000 women die from the consequences of breast cancer. Current imaging modalities are
not optimal in discriminating benign from malignant tissue. Visualizing the malignancy-associated increased
hemoglobin concentration might significantly improve early diagnosis of breast cancer. Since photoacoustic imaging
can visualize hemoglobin in tissue with optical contrast and ultrasound-like resolution, it is potentially an ideal method
for early breast cancer imaging.
The Twente Photoacoustic Mammoscope (PAM) has been developed specifically for breast imaging. Recently, a
large clinical study has been started in the Medisch Spectrum Twente in Oldenzaal using PAM. In PAM, the breast is
slightly compressed between a window for laser light illumination and a flat array ultrasound detector. The
measurements are performed using a Q-switched Nd:YAG laser, pulsed at 1064 nm and a 1 MHz unfocused ultrasound
detector array. Three-dimensional data are reconstructed using a delay and sum reconstruction algorithm. Those
reconstructed images are compared with conventional imaging and histopathology. In the first phase of the study 12
patients with a malignant lesion and 2 patients with a benign cyst have been measured. The results are used to guide
developments in photoacoustic mammography in order to pave the way towards an optimal technique for early diagnosis
of breast cancer.
Tissue mimicking phantoms are important for performance evaluation of imaging systems: in photoacoustics they need
to accomplish both soft tissue optical and acoustic properties. PVA gels by freezing-thawing (F-T) have been used to
simulate tissue properties. The microstructure, dependent on rate and extent of temperature cycling, is responsible for
optical and acoustic properties. In F-T of larger phantoms, temperature differences in the mass are expected, resulting in
a likely inhomogeneous distribution of properties in the phantom. We investigated speed of sound, acoustic attenuation,
reduced optical scattering coefficient and microstructure: their variations are correlated with thermal differences between
phantom surface and bulk.
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