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Cardiac interventional procedures are often performed under fluoroscopic guidance, exposing both the patient and operators to ionizing radiation. To reduce this risk of radiation exposure, we are exploring the use of photoacoustic imaging paired with robotic visual servoing for cardiac catheter visualization and surgical guidance. A cardiac catheterization procedure was performed on two in vivo swine after inserting an optical fiber into the cardiac catheter to produce photoacoustic signals from the tip of the fiber-catheter pair. A combination of photoacoustic imaging and robotic visual servoing was employed to visualize and maintain constant sight of the catheter tip in order to guide the catheter through the femoral or jugular vein, toward the heart. Fluoroscopy provided initial ground truth estimates for 1D validation of the catheter tip positions, and these estimates were refined using a 3D electromagnetic-based cardiac mapping system as the ground truth. The 1D and 3D root mean square errors ranged 0.25-2.28 mm and 1.24-1.54 mm, respectively. The catheter tip was additionally visualized at three locations within the heart: (1) inside the right atrium, (2) in contact with the right ventricular outflow tract, and (3) inside the right ventricle. Lasered regions of cardiac tissue were resected for histopathological analysis, which revealed no laser-related tissue damage, despite the use of 2.98 mJ per pulse at the fiber tip (379.2 mJ/cm2 fluence). In addition, there was a 19 dB difference in photoacoustic signal contrast when visualizing the catheter tip pre- and post-endocardial tissue contact, which is promising for contact confirmation during cardiac interventional procedures (e.g., cardiac radiofrequency ablation). These results are additionally promising for the use of photoacoustic imaging to guide cardiac interventions by providing depth information and enhanced visualization of catheter tip locations within blood vessels and within the beating heart.

Many cardiac interventional procedures (e.g., radiofrequency ablation) require fluoroscopy to navigate catheters in veins toward the heart. However, this image guidance method lacks depth information and increases the risks of radiation exposure for both patients and operators. To overcome these challenges, we developed a robotic visual servoing system that maintains visualization of segmented photoacoustic signals from a cardiac catheter tip. This system was tested in two in vivo cardiac catheterization procedures with ground truth position information provided by fluoroscopy and electromagnetic tracking. The 1D root mean square localization errors within the vein ranged 1.63 − 2.28 mm for the first experiment and 0.25 − 1.18 mm for the second experiment. The 3D root mean square localization error for the second experiment ranged 1.24 − 1.54 mm. The mean contrast of photoacoustic signals from the catheter tip ranged 29.8 − 48.8 dB when the catheter tip was visualized in the heart. Results indicate that robotic-photoacoustic imaging has promising potential as an alternative to fluoroscopic guidance. This alternative is advantageous because it provides depth information for cardiac interventions and enables enhanced visualization of the catheter tips within the beating heart.

Liver surgeries carry considerable risk of injury to major blood vessels, which can lead to hemorrhaging and possibly patient death. Photoacoustic imaging is one solution to enable intraoperative visualization of blood vessels, which has the potential to reduce the risk of accidental injury to these blood vessels during surgery. This paper presents our initial results of a feasibility study, performed during laparotomy procedures on two pigs, to determine in vivo vessel visibility for photoacoustic-guided liver surgery. Delay-and-sum beamforming and coherence-based beamforming were used to display photoacoustic images and differentiate the signal inside blood vessels from surrounding liver tissue. Color Doppler was used to confirm vessel locations. Results lend insight into the feasibility of photoacoustic-guided liver surgery when the ultrasound probe is fixed and the light source is used to interrogate the surgical workspace.

Abdominal surgeries carry considerable risk of gastrointestinal and intra-abdominal hemorrhage, which could possibly cause patient death. Photoacoustic imaging is one solution to overcome this challenge by providing visualization of major blood vessels during surgery. We investigate the feasibility of in vivo blood vessel visualization for photoacoustic-guided liver and pancreas surgeries. In vivo photoacoustic imaging of major blood vessels in these two abdominal organs was successfully achieved after a laparotomy was performed on two swine. Three-dimensional photoacoustic imaging with a robot-controlled ultrasound (US) probe and color Doppler imaging were used to confirm vessel locations. Blood vessels in the in vivo liver were visualized with energies of 20 to 40 mJ, resulting in 10 to 15 dB vessel contrast. Similarly, an energy of 36 mJ was sufficient to visualize vessels in the pancreas with up to 17.3 dB contrast. We observed that photoacoustic signals were more focused when the light source encountered a major vessel in the liver. This observation can be used to distinguish major blood vessels in the image plane from the more diffuse signals associated with smaller blood vessels in the surrounding tissue. A postsurgery histopathological analysis was performed on resected pancreatic and liver tissues to explore possible laser-related damage. Results are generally promising for photoacoustic-guided abdominal surgery when the US probe is fixed and the light source is used to interrogate the surgical workspace. These findings are additionally applicable to other procedures that may benefit from photoacoustic-guided interventional imaging of the liver and pancreas (e.g., biopsy and guidance of radiofrequency ablation lesions in the liver).

Directly displaying the spatial coherence of photoacoustic signals (i.e., coherence-based photoacoustic imaging) remarkably improves image contrast, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and imaging depth when compared to conventional amplitude-based reconstruction techniques (e.g., backprojection, delay-and-sum beamforming, and Fourier-based reconstruction). We recently developed photoacoustic-specific theory to describe the spatial coherence process as a function of the element spacing on a receive acoustic aperture to enable photoacoustic image optimization without requiring experiments. However, this theory lacked noise models, which contributed to significant departures in coherence measurements when compared to experimental data, particularly at higher values of element separation. In this paper, we develop and implement two models based on experimental observations of noise in photoacoustic spatial coherence measurements to improve our existing spatial coherence theory. These models were derived to describe the effects of incident fluence variations, low-energy light sources (e.g., pulsed laser diodes and light-emitting diodes), averaging multiple signals from low-energy light sources, and imaging with light sources that are > 5mm from photoacoustic targets. Results qualitatively match experimental coherence functions and provide similar contrast, SNR, and CNR to experimental SLSC images. In particular, the added noise affects image quality metrics by introducing large variations in target contrast and significantly reducing target CNR and SNR when compared to minimal-noise cases. These results provide insight into additional requirements for optimization of coherence-based photoacoustic image quality.

Neuron differentiation is a complex process involving various cell-cell interactions, and multiple signaling pathways. We showed previously that CD40 is expressed and functional on mouse and human neurons. In neurons, ligation of CD40 protects against serum withdrawal-induced injury and plays a role in survival and differentiation. CD40 deficient mice display neuron dysfunction, aberrant neuron morphologic changes, and associated gross brain abnormalities. Previous studies by Tone and colleagues suggested that five isoforms of CD40 exist with two predominant isoforms expressed in humans: signal-transducible CD40 type I and a C-terminal truncated, non-signal-transducible CD40 type II. We hypothesized that differential expression of CD40 isoform type I and type II in neurons may modulate neuron differentiation. Results show that adult wild-type, and CD40{sup -/-} deficient mice predominantly express CD40 type I and II isoforms. Whereas adult wild-type mice express mostly CD40 type I in cerebral tissues at relatively high levels, in age and gender-matched CD40{sup -/-} mice CD40 type I expression was almost completely absent; suggesting a predominance of the non-signal-transducible CD40 type II isoform. Younger, 1 day old wild-type mice displayed less CD40 type I, and more CD40 type II, as well as, greater expression of soluble CD40 (CD40L/CD40 signal inhibitor), compared withmore » 1 month old mice. Neuron-like N2a cells express CD40 type I and type II isoforms while in an undifferentiated state, however once induced to differentiate, CD40 type I predominates. Further, differentiated N2a cells treated with CD40 ligand express high levels of neuron specific nuclear protein (NeuN); an effect reduced by anti-CD40 type I siRNA, but not by control (non-targeting) siRNA. Altogether these data suggest that CD40 isoforms may act in a temporal fashion to modulate neuron differentiation during brain development. Thus, modulation of neuronal CD40 isoforms and CD40 signaling may represent important therapeutic modalities for neurodegenerative and neurodevelopmental disorders, as well as, for enhancement of neurogenesis.« less