Universal Hand-held Three-dimensional Optoacoustic Imaging Probe for Deep Tissue Human Angiography and Functional Preclinical Studies in Real Time

The overall goal of the following experiment is to illustrate the imaging capabilities of a newly developed handheld opto acoustic system for three dimensional, functional and molecular imaging in real time. This is achieved using a probe with a spherical matrix array of pizo, electric transducers around a fiber bundle that guides light pulses when held against tissue. Nanosecond duration, pulses of light excite ultrasonic responses that are captured by the probe.

Next, the data is used to perform real-time image reconstruction, allowing scans in a handheld mode. The results show the feasibility of deep tissue imaging of vascular morphology, as well as important hemodynamic and perfusion parameters with a portable system. The particular focus of all laboratory is development of novel biomedical imaging tools based on optic acoustics, diffuse optics, ultrasound, and multimodality approaches.

The newly developed handheld optic acoustic tomography system can essentially provide truly five dimensional imaging capability. This means it can deliver high resolution spectrally enriched volumetric imaging of tissue morphology and function in real time. The volumetric hand imaging approach combined with real-time function, eliminating capacity come with important advantages for clinical diagnostics.

For example, in peripheral vascular disease, lymphatic system disorders, breast cancer, skin lesions, inflammation, arthritis. Combined with fast wavelength tuning laser technology, the system enables real-time imaging of bio distribution of photo absorbing agents. This is why new possibilities may equally emerge in small animal molecular imaging applications.

For example, studying tissue hemodynamics in vivo cell tracking, visualization of pharmacokinetics, organ perfusion, or neuro imaging Begin by preparing the hardware. Turn on the tunable near infrared laser source for a warmup period of about 15 minutes. To stabilize its output, the laser output will be connected to the handheld probe.

The probe consists of a matrix array of piso electric elements arranged to cover part of a sphere with an opening for a fiber bundle. At the center, connect a fiber bundle to guide the laser beam from the laser output to the handheld probe. Next, connect the spherical matrix detection array of the handheld probe to the parallel data acquisition system, which is triggered by the Q switch Output of the laser continue by preparing the acoustic coupling for the probe.

The transducer has a matching casing capped with an optically and acoustically transparent polyethylene membrane, which will make contact with the skin and close the active transducer surface with the casing. The relative position of the active detection surface with respect to the tissue surface determines the effective imaging depth. Connect a pump between the tank and the probe.

Then use it to fill the approximately 100 milliliter volume between the transducer and the membrane. Once the pumping is complete, disconnect the pump. Inspect the probe to ensure there are no air bubbles or leaks.

Now for safety, put on protective goggles, appropriate for near infrared wavelengths. Proceed by setting the imaging wavelengths and laser pulse repetition rate. In the control software, the wavelength range is 690 to 900 nanometers with the optical choice, depending on the particular tissue, chromo, fours, and extrinsically administered agents of interest.

The pulse repetition rate is in the range of 10 to 50 hertz and depends on the desired volumetric imaging frame rate, but is also limited by the laser exposure limits. Also, set the acoustic data acquisition system to have one mega ohm input impedance with a sampling rate of 40 mega samples per second and 12 bit vertical resolution. For safe operations.

Measure exposure levels in the near infrared spectral region with a laser power meter. Place the power meter at the polyethylene membrane of the probe for the measurement. Pass laser radiation through the probe and adjust the laser power and repetition rate.

So to meet safe exposure levels at the membrane when adjustments are made, then remove the power meter. The probe is ready for use. The next step is to prepare the patient for the procedure.

Provide the patient with protective goggles appropriate for near infrared wavelengths. Inspect the region to be imaged. If hair is present, apply a depletion lotion to remove it and avoid undesired background in the images.

Clear the region with a wet tissue. Once the region is clear, apply ultrasound gel on the skin in the area that is to be imaged. To provide efficient acoustic coupling.

Keep the probe in place and start the preview software, which enables laser output and allows visualizing three dimensional images. The frame rate of the opto acoustic images corresponds to the laser pulse repetition rate and is displayed in real time. When tomographic reconstruction is implemented on a graphics processing unit, gently move the probe to optimize visualization and to locate the structure of interest.

Continue to use the preview software and switch the hardware into data acquisition mode on the patient. Gently move the probe a few millimeters per second around the imaged region to track the structures of interest. On completion of data acquisition, stop the software, which also stops the laser.

The forearm of a healthy volunteer is on the left. The white box represents the region visualized with the probe. On the right are the maximum intensity projection images of the probed region.

As the probe was scanned slowly over the forearm, real-time visualization of the vessels was achieved for all scanning positions. The images used 800 nanometers light with the laser pulse repetition rate of 10 hertz. Multi-spectral imaging was performed by scanning the probe along the wrist of a healthy volunteer.

A 50 hertz laser pulse repetition rate was used in conjunction with a per pulse wavelength tuning. The wavelengths used were between 730 nanometers and 850 nanometers in 30 nanometer steps. At the lower right are spectrally unmixed images showing the distribution of oxygenated hemoglobin in red, deoxygenated hemoglobin in blue, and melanin in yellow.

Under the assumption that only these components are responsible for absorption as the probe scans the wrist, the distribution of these three tissue chromophores can be tracked in real time. This movie demonstrates the ability of the probe to follow dynamic processes. Circulation in the middle finger was obstructed with a rubber band and released during data acquisition.

Appearance of the scissors indicates the moment when the rubber band was removed. Data was collected at 10 frames per second at 900 nanometers wavelength. The handheld imaging procedure can be mastered in a very short time, and since other clinical imaging modalities are not able to deliver volumetric with comparable time resolution, we are confident that the presented system will attain new value for accurate diagnostics and treatment monitoring Motion artifacts may still severely affect the performance and image quality when using the probe in the handheld mode.

As a rule of thumb, motion velocity shall not exceed three millimeters per second. If a laser repetition rate of 10 hertz is used in combination with multim data acquisition, of course, faster motion is allowed. If a higher repetition rate laser is employed With a new imaging approach, we hope to enable new biological discoveries.

We would also like to offer physicians a new tool for clinical diagnostics in multiple indications. For example, cardiovascular and peripheral vascular disease disorders related to the lymphatic system, breast lesions, arthritis and inflammation.