John Gamelin

A real-time photoacoustic tomography system for small animals

A real-time 512-element photoacoustic tomography system for small animal imaging using a ring ultrasound array has been developed. The system, based upon a 5 MHz transducer array formed along a 50 mm circular aperture, achieves sub-200 micron lateral resolution over a 2 cm disk-shaped region. Corresponding elevation resolutions of 0.6 to 2.5 mm over the central volume enable depth-resolved 3D tomographic imaging with linear translation. Using 8:1 electronic multiplexing, imaging at up to 8 frame/sec is demonstrated for both dynamic phantoms and in vivo mouse and brain samples. The real-time, full 2D tomographic capability of the system paves the way for functional photoacoustic tomographic imaging studies in small animals with sub-second time frame.

Real-time photoacoustic tomography of cortical hemodynamics in small animals

For the first time, the hemodynamics within the entire cerebral cortex of a mouse were studied by using photoacoustic tomography (PAT) in real time. The PAT system, based on a 512-element full-ring ultrasound array, received photoacoustic signals primarily from a slice of 2-mm thickness. This system can provide high-resolution brain vasculature images. We also monitored the fast wash-in process of a photoacoustic contrast agent in the mouse brain. Our results demonstrated that PAT is a powerful imaging modality that can be potentially used to study small animal neurofunctional activities.

Coregistered three-dimensional ultrasound and photoacoustic imaging system for ovarian tissue characterization

Ovarian cancer has the highest mortality of all gynecologic cancers, with a five-year survival rate of only 30% or less. Current imaging techniques are limited in sensitivity and specificity in detecting early stage ovarian cancer prior to its widespread metastasis. New imaging techniques that can provide functional and molecular contrasts are needed to reduce the high mortality of this disease. One such promising technique is photoacoustic imaging. We develop a 1280-element coregistered 3-D ultrasound and photoacoustic imaging system based on a 1.75-D acoustic array. Volumetric images over a scan range of 80 deg in azimuth and 20 deg in elevation can be achieved in minutes. The system has been used to image normal porcine ovarian tissue. This is an important step toward better understanding of ovarian cancer optical properties obtained with photoacoustic techniques. To the best of our knowledge, such data are not available in the literature. We present characterization measurements of the system and compare coregistered ultrasound and photoacoustic images of ovarian tissue to histological images. The results show excellent coregistration of ultrasound and photoacoustic images. Strong optical absorption from vasculature, especially highly vascularized corpora lutea and low absorption from follicles, is demonstrated.

Optimal probing of optical contrast of breast lesions of different size located at different depths by US localization

We report a frequency domain optical tomography system utilizing three RF modulation frequencies, which are optimized for probing breast lesions of different size located at different depths. A real-time co-registered ultrasound scanner is used to provide on-site estimation of lesion size and location. Based on the lesion information, an optimal light modulation frequency can be selected, which may yield more accurate estimates of lesion angiogenesis and hypoxia. Phantom experiments have demonstrated that a high modulation frequency, such as 350Mhz, is preferable for probing small lesions closer to the surface while a low modulation frequency, such as 50Mhz, is desirable for imaging deeper and larger lesions. A clinical example of a large invasive carcinoma is presented to demonstrate the application of this novel technique.

Mechanisms of the ultrasonic modulation of fluorescence in turbid media

To understand the modulation mechanisms of fluorescence emission induced by ultrasonic waves in turbid media, a mathematical model is proposed and compared with the recent experimental observations of Kobayashi et al. [Appl. Phys. Lett. 89, 181102 (2006)]. Modulation of fluorophore concentration is considered as the source of the oscillation of fluorescence signals when fluorophore concentration is low enough so that quenching effects can be ignored. By solving the rate equation and photon diffusion equation, quantitative solutions are given to quantify the modulation strength. Our calculations predict that the modulation depth (the ratio of the modulated signal strength to the unmodulated signal strength) can reach 10(-4) when ultrasonic pressure with the order of magnitude of megapascals is applied in the ultrasound focal zone. Our model explains the relationship between the modulation strength and the average fluorophore concentration and also predicts a method to measure or image fluorescence lifetime in the turbid medium. When fluorophore concentration is high enough so that fluorescence quenching occurs, the fluorescence modulation is attributed to the modulation of quenching efficiency. Quenching caused by fluorescence resonance energy transfer can lead to a nonlinear relationship between the modulation fluorescence strength and the applied ultrasound strength.

Target detection and quantification using a hybrid hand-held diffuse optical tomography and photoacoustic tomography system.

We present a photoacoustic tomography-guided diffuse optical tomography approach using a hand-held probe for detection and characterization of deeply-seated targets embedded in a turbid medium. Diffuse optical tomography guided by coregistered ultrasound, MRI, and x ray has demonstrated a great clinical potential to overcome lesion location uncertainty and to improve light quantification accuracy. However, due to the different contrast mechanisms, some lesions may not be detectable by a nonoptical modality but yet have high optical contrast. Photoacoustic tomography utilizes a short-pulsed laser beam to diffusively penetrate into tissue. Upon absorption of the light by the target, photoacoustic waves are generated and used to reconstruct, at ultrasound resolution, the optical absorption distribution that reveals optical contrast. However, the robustness of optical property quantification of targets by photoacoustic tomography is complicated because of the wide range of ultrasound transducer sensitivity, the orientation and shape of the targets relative to the ultrasound array, and the uniformity of the laser beam. We show in this paper that the relative optical absorption map provided by photoacoustic tomography can potentially guide the diffuse optical tomography to accurately reconstruct target absorption maps.

Photoacoustic tomography of small animal brain with a curved array transducer

We present the application of a curved array photoacoustic tomographic imaging system that can provide rapid, high-resolution photoacoustic imaging of small animal brains. The system is optimized to produce a B-mode, 90-deg field-of-view image at sub-200-microm resolution at a frame rate of approximately 1 frame/second when a 10-Hz pulse repetition rate laser is employed. By rotating samples, a complete 360-deg scan can be achieved within 15 s. In previous work, two-dimensional (2-D) ex vivo mouse brain cortex imaging has been reported. We report three-dimensional (3-D) small animal brain imaging obtained with the curved array system. The results are presented as a series of 2-D cross-sectional images. Besides structural imaging, the blood oxygen saturation of the animal brain cortex is also measured in vivo. In addition, the system can measure the time-resolved relative changes in blood oxygen saturation level in the small animal brain cortex. Last, ultrasonic gel coupling, instead of the previously adopted water coupling, is conveniently used in near-real-time 2-D imaging.

Fluorescence imaging of vascular endothelial growth factor in tumors for mice embedded in a turbid medium

We demonstrate the feasibility of fluorescence imaging of deeply seated tumors using mice injected with an angiogenesis tracer, a vascular endothelial growth factor conjugated with the infrared dye cyanine 7 (VEGF/Cy7). Our optical-only imaging reconstruction method separately estimates the target depth, and then applies this information to reconstruct functional information such as fluorophore concentration. Fluorescence targets with concentrations as low as sub-25 nM are well reconstructed at depths up to 2 cm in both homogeneous and heterogeneous media with this technique.

A prototype hybrid intraoperative probe for ovarian cancer detection

A novel prototype intraoperative system combining positron detection and optical coherence tomography (OCT) imaging has been developed for early ovarian cancer detection. The probe employs eight plastic scintillating fiber tips for preferential detection of local positron activity surrounding a central scanning OCT fiber providing volumetric imaging of tissue structure in regions of high radiotracer uptake. Characterization measurements of positron sensitivity, spatial response, and position mapping are presented for Tl(204)/Cs(137) sources as well as 18F-FDG. In conjunction with co-registered frequency domain OCT measurements the results demonstrate the potential for a miniaturized laparoscopic probe offering simultaneous functional localization and structural imaging for improved early cancer detection.

Fast, limited-data photoacoustic imaging for multiplexed systems using a frequency-domain estimation technique

PURPOSE A new frequency-domain estimation algorithm has been developed that uses a priori information to simultaneously improve imaging quality and time resolution in photoacoustic tomography with incomplete data sets. METHODS The method involves application of a single-stage Wiener optimal filter to augment data sets by interpolation between measurement locations using relationships determined in a reference scan. The filter can be applied in real-time using FFT methods using either fixed or dynamic references and used with any imaging algorithm. The performance of the method is compared to a modified version of constrained backprojection algorithms using simulations and experimental investigations. RESULTS Simulations demonstrate the effectiveness of the approach for tracking dynamic photoacoustic activity for data sets with limited views (90 degrees) or tomographic views with a reduced number of acquisition angles at any given time (< or = 32). Experimental data of contrast uptake and washout using a 512-element curved transducer with 8:1 electronic multiplexing with the algorithm demonstrate full two-dimensional tomographic imaging with a temporal resolution better than 130 ms. CONCLUSIONS The estimation algorithm enables high spatial resolution, real-time imaging of dynamic physiological events or volumetric regions for photoacoustic systems employing multiplexing or scanning.