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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.

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).

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