Robert A. Kruger

Photoacoustic angiography of the breast

PURPOSE The authors report a noninvasive technique and instrumentation for visualizing vasculature in the breast in three dimensions without using either ionizing radiation or exogenous contrast agents, such as iodine or gadolinium. Vasculature is visualized by virtue of its high hemoglobin content compared to surrounding breast parenchyma. The technique is compatible with dynamic contrast-enhanced studies. METHODS Photoacoustic sonic waves were stimulated in the breast with a pulsed laser operating at 800 nm and a mean exposure of 20 mJ/pulse over an area of approximately 20 cm2. These waves were subsequently detected by a hemispherical array of piezoelectric transducers, the temporal signals from which were filtered and backprojected to form three-dimensional images with nearly uniform k-space sampling. RESULTS Three-dimensional vascular images of a human volunteer demonstrated a clear visualization of vascular anatomy with submillimeter spatial resolution to a maximum depth of 40 mm using a 24 s image acquisition protocol. Spatial resolution was nearly isotropic and approached 250 microm over a 64 x 64 x 50 mm field of view. CONCLUSIONS The authors have successfully visualized submillimeter breast vasculature to a depth of 40 mm using an illumination intensity that is 32 times less than the maximum permissible exposure according to the American National Standard for Safe Use of Lasers. Clearly, the authors can achieve greater penetration depth in the breast by increasing the intensity and the cross-sectional area of the illumination beam. Given the 24 s image acquisition time without contrast agent, dynamic, contrast-enhanced, photoacoustic breast imaging using optically absorbing contrast agents is conceivable in the future.

Thermoacoustic molecular imaging of small animals.

We have designed, constructed, and tested a thermoacoustic computed tomography (TCT) scanner for imaging optical absorption in small animals in three dimensions. The device utilizes pulsed laser irradiation (680-1064 nm) and a unique, 128-element transducer array. We quantified the isotropic spatial resolution of this scanner to be 0.35 mm. We describe a dual-wavelength subtraction technique for isolating optical dyes with TCT. Phantom experiments demonstrate that we can detect 5 fmol of a near-infrared dye (indocyanine green, ICG) in a 1-microL volume using dual-wavelength subtraction. Initial TCT imaging in phantoms and in two sacrificed mice suggests that three-dimensional, optical absorption patterns in small animals can be detected with an order of magnitude better spatial resolution and an order of magnitude better low-contrast detectability in small animals when compared to fluorescence imaging or diffusion optical tomography.

Time resolved imaging through a highly scattering medium

Transmission images through a highly scattering medium have been obtained using picosecond pulses of visible light. The imaging method involves recording and discriminating between the times-of-flight of photons that penetrate th medium and using a fraction of the light with the shortest travel times to construct an image. The technique is being developed as a possible alternative method of screening for breast cancer without using potentially harmful x-rays. One- and two-dimensional images are presented of objects whose optical thicknesses are comparable with those of the human breast at visible wavelengths.

Computerized Fluoroscopy in Real Time for Noninvasive Visualization of the Cardiovascular System

A computerized fluoroscopic system with dedicated real-time hard-wired algorithms can be used for cardiovascular imaging with or without injection of iodine. Initial differentiated and integrated time subtraction displays are presented. Contrast studies appear adequate for visualization of cardiovascular dynamics. Cardiac images without contrast material suggest expected blood flow patterns but are difficult to interpret.

Scatter estimation for a digital radiographic system using convolution filtering.

The use of a convolution-filtering method to estimate the scatter distribution in images acquired with a digital subtraction angiography (DSA) imaging system has been studied. Investigation of more than 175 convolution kernels applied to images of anthropomorphic head, chest, and pelvic phantoms using 15-, 25-, and 36-cm fields of view (digitized onto a 512 X 512 pixel image matrix) showed that two-dimensional exponential kernels with a full width at half maximum (FWHM) of 50-150 pixels best reproduced the scatter fields within these images with a root-mean-square percentage error from 4% to 8%. A two-dimensional exponential kernal with a FWHM of 75 pixels in each dimension applied to ten different anatomic presentations and fields of view, resulted in an average root-mean-square percentage error of 6.6% for the ten cases studied. The method should be implementable using an array of small lead beam stops placed in the field of only a single mask image and the above described convolution kernel applied to both mask and postopacification images. The mask beam-stop data are used to scale both mask and postopacification convolution-filtered images. This scaled, convolution-filtered image is then subtracted from the original image to produce a largely scatter-corrected image.

Dedicated 3D photoacoustic breast imaging

PURPOSE To report the design and imaging methodology of a photoacoustic scanner dedicated to imaging hemoglobin distribution throughout a human breast. METHODS The authors developed a dedicated breast photoacoustic mammography (PAM) system using a spherical detector aperture based on our previous photoacoustic tomography scanner. The system uses 512 detectors with rectilinear scanning. The scan shape is a spiral pattern whose radius varies from 24 to 96 mm, thereby allowing a field of view that accommodates a wide range of breast sizes. The authors measured the contrast-to-noise ratio (CNR) using a target comprised of 1-mm dots printed on clear plastic. Each dot absorption coefficient was approximately the same as a 1-mm thickness of whole blood at 756 nm, the output wavelength of the Alexandrite laser used by this imaging system. The target was immersed in varying depths of an 8% solution of stock Liposyn II-20%, which mimics the attenuation of breast tissue (1.1 cm(-1)). The spatial resolution was measured using a 6 μm-diameter carbon fiber embedded in agar. The breasts of four healthy female volunteers, spanning a range of breast size from a brassiere C cup to a DD cup, were imaged using a 96-mm spiral protocol. RESULTS The CNR target was clearly visualized to a depth of 53 mm. Spatial resolution, which was estimated from the full width at half-maximum of a profile across the PAM image of a carbon fiber, was 0.42 mm. In the four human volunteers, the vasculature was well visualized throughout the breast tissue, including to the chest wall. CONCLUSIONS CNR, lateral field-of-view and penetration depth of our dedicated PAM scanning system is sufficient to image breasts as large as 1335 mL, which should accommodate up to 90% of the women in the United States.

Photoacoustic ultrasound: Pulse production and detection in 0.5% Liposyn

Theoretical predictions and experimental measurements of photoacoustic pulse production within a 0.5% solution of Liposyn, a highly scattering, optical propagation medium, are reported. A simple model for photoacoustic energetics is developed that predicts photoacoustic signal pressure as a function of depth within a turbid medium following surface irradiation from an infrared source. The model is valid for very short irradiation duration. The model predicts that the acoustic pressure produced at a distance r from the center of a small, highly absorbing sphere of radius R consists of two, opposite polarity pulses, one originating from the near and one from the far side of the sphere. The magnitude of these biphasic pulses is expected to be proportional to the energy fluence (E) incident on the surface of the sphere and to the ratio, R/r. Furthermore, the energy fluence (E) that reaches the sphere is roughly proportional to e-mu effZ, where mu eff is the effective attenuation coefficient of the turbid medium and Z is the depth of the embedded sphere below the irradiated surface. The variation of E with depth within the absorber and biphasic acoustic pulse production have been verified experimentally. Further experiments demonstrate that a small (3-mm diameter), highly absorbing sphere can be detected and localized at a depth of 37.5 mm within a 0.5% solution of Liposyn with a spatial resolution of 1 x 6 mm2, using a biologically safe level of infrared irradiation (lambda = 1064 nm) and a conventional ultrasound transducer (frequency = 2.25 MHz). These results suggest that photoacoustic ultrasound imaging may have application to biologic systems such as the human breast.

Computerized fluoroscopy techniques for intravenous study of cardiac chamber dynamics

A computerized fluoroscopy system which was recently developed in our laboratories permits image contrast increases of 8-16 relative to conventional image intensifer fluoroscopy and permits study of canine and human ventricular wall motion using peripheral intravenous injections. Two time-dependent image subtraction algorithms are illustrated in connection with observation of artificially infarcted dog hearts. The first algorithm produces a display analogous to direct ventriculography using catheterization. The second displays regions of dyskinetic motion as anomalous image grey shades.

A Digital Video Image Processor for Real-Time X-Ray Subtraction Imaging

A digital video image processor (VIP) has been constructed and is presently being tested and used in a variety of preclinical medical imaging situations. Details of its design are discussed. The VIP can digitize, store and process images from a conventional radiographic TV fluoroscopy system. From these images a variety of subtraction images can be formed and displayed in real time at video rates. These subtraction images include: K-edge images, time dependent subtraction images, tomographic, and K-edge tomographic images. Examples of in vivo K-edge and time-dependent subtraction images are presented.

Digital K-edge subtraction radiography.

K-edge subtraction images have been produced using a digital video image processor. Images formed by three filtered x-ray beams are detected by an image intensifier-Plumbicon system, digitilized, and combined in real time to produce bone- and tissue-free K-edge subtraction images of iodinated structures. Preliminary studies of rhesus monkey cranial, spinal, and abdominal structures are compared with those of conventional radiography.