Daniil I. Nikitichev

Performance characteristics of an interventional multispectral photoacoustic imaging system for guiding minimally invasive procedures

Abstract. Precise device guidance is important for interventional procedures in many different clinical fields including fetal medicine, regional anesthesia, interventional pain management, and interventional oncology. While ultrasound is widely used in clinical practice for real-time guidance, the image contrast that it provides can be insufficient for visualizing tissue structures such as blood vessels, nerves, and tumors. This study was centered on the development of a photoacoustic imaging system for interventional procedures that delivered excitation light in the ranges of 750 to 900 nm and 1150 to 1300 nm, with an optical fiber positioned in a needle cannula. Coregistered B-mode ultrasound images were obtained. The system, which was based on a commercial ultrasound imaging scanner, has an axial resolution in the vicinity of 100  μm and a submillimeter, depth-dependent lateral resolution. Using a tissue phantom and 800 nm excitation light, a simulated blood vessel could be visualized at a maximum distance of 15 mm from the needle tip. Spectroscopic contrast for hemoglobin and lipids was observed with ex vivo tissue samples, with photoacoustic signal maxima consistent with the respective optical absorption spectra. The potential for further optimization of the system is discussed.

From medical imaging data to 3D printed anatomical models

Anatomical models are important training and teaching tools in the clinical environment and are routinely used in medical imaging research. Advances in segmentation algorithms and increased availability of three-dimensional (3D) printers have made it possible to create cost-efficient patient-specific models without expert knowledge. We introduce a general workflow that can be used to convert volumetric medical imaging data (as generated by Computer Tomography (CT)) to 3D printed physical models. This process is broken up into three steps: image segmentation, mesh refinement and 3D printing. To lower the barrier to entry and provide the best options when aiming to 3D print an anatomical model from medical images, we provide an overview of relevant free and open-source image segmentation tools as well as 3D printing technologies. We demonstrate the utility of this streamlined workflow by creating models of ribs, liver, and lung using a Fused Deposition Modelling 3D printer.

Interventional Photoacoustic Imaging of the Human Placenta with Ultrasonic Tracking for Minimally Invasive Fetal Surgeries

Image guidance plays a central role in minimally invasive fetal surgery such as photocoagulation of inter-twin placental anastomosing vessels to treat twin-to-twin transfusion syndrome (TTTS). Fetoscopic guidance provides insufficient sensitivity for imaging the vasculature that lies beneath the fetal placental surface due to strong light scattering in biological tissues. Incomplete photocoagulation of anastamoses is associated with postoperative complications and higher perinatal mortality. In this study, we investigated the use of multi-spectral photoacoustic (PA) imaging for better visualization of the placental vasculature. Excitation light was delivered with an optical fiber with dimensions that are compatible with the working channel of a fetoscope. Imaging was performed on an ex vivo normal term human placenta collected at Caesarean section birth. The photoacoustically-generated ultrasound signals were received by an external clinical linear array ultrasound imaging probe. A vein under illumination on the fetal placenta surface was visualized with PA imaging, and good correspondence was obtained between the measured PA spectrum and the optical absorption spectrum of deoxygenated blood. The delivery fiber had an attached fiber optic ultrasound sensor positioned directly adjacent to it, so that its spatial position could be tracked by receiving transmissions from the ultrasound imaging probe. This study provides strong indications that PA imaging in combination with ultrasonic tracking could be useful for detecting the human placental vasculature during minimally invasive fetal surgery.

Coded excitation ultrasonic needle tracking: An in vivo study

PURPOSE Accurate and efficient guidance of medical devices to procedural targets lies at the heart of interventional procedures. Ultrasound imaging is commonly used for device guidance, but determining the location of the device tip can be challenging. Various methods have been proposed to track medical devices during ultrasound-guided procedures, but widespread clinical adoption has remained elusive. With ultrasonic tracking, the location of a medical device is determined by ultrasonic communication between the ultrasound imaging probe and a transducer integrated into the medical device. The signal-to-noise ratio (SNR) of the transducer data is an important determinant of the depth in tissue at which tracking can be performed. In this paper, the authors present a new generation of ultrasonic tracking in which coded excitation is used to improve the SNR without spatial averaging. METHODS A fiber optic hydrophone was integrated into the cannula of a 20 gauge insertion needle. This transducer received transmissions from the ultrasound imaging probe, and the data were processed to obtain a tracking image of the needle tip. Excitation using Barker or Golay codes was performed to improve the SNR, and conventional bipolar excitation was performed for comparison. The performance of the coded excitation ultrasonic tracking system was evaluated in an in vivo ovine model with insertions to the brachial plexus and the uterine cavity. RESULTS Coded excitation significantly increased the SNRs of the tracking images, as compared with bipolar excitation. During an insertion to the brachial plexus, the SNR was increased by factors of 3.5 for Barker coding and 7.1 for Golay coding. During insertions into the uterine cavity, these factors ranged from 2.9 to 4.2 for Barker coding and 5.4 to 8.5 for Golay coding. The maximum SNR was 670, which was obtained with Golay coding during needle withdrawal from the brachial plexus. Range sidelobe artifacts were observed in tracking images obtained with Barker coded excitation, and they were visually absent with Golay coded excitation. The spatial tracking accuracy was unaffected by coded excitation. CONCLUSIONS Coded excitation is a viable method for improving the SNR in ultrasonic tracking without compromising spatial accuracy. This method provided SNR increases that are consistent with theoretical expectations, even in the presence of physiological motion. With the ultrasonic tracking system in this study, the SNR increases will have direct clinical implications in a broad range of interventional procedures by improving visibility of medical devices at large depths.

Real-Time Needle Guidance with Photoacoustic and Laser-Generated Ultrasound Probes

Detection of tissue structures such as nerves and blood vessels is of critical importance during many needle-based minimally invasive procedures. For instance, unintentional injections into arteries can lead to strokes or cardiotoxicity during interventional pain management procedures that involve injections in the vicinity of nerves. Reliable detection with current external imaging systems remains elusive. Optical generation and reception of ultrasound allow for depth-resolved sensing and they can be performed with optical fibers that are positioned within needles used in clinical practice. The needle probe developed in this study comprised separate optical fibers for generating and receiving ultrasound. Photoacoustic generation of ultrasound was performed on the distal end face of an optical fiber by coating it with an optically absorbing material. Ultrasound reception was performed using a high-finesse Fabry-Pérot cavity. The sensor data was displayed as an M-mode image with a real-time interface. Imaging was performed on a biological tissue phantom.

Fiber optic photoacoustic probe with ultrasonic tracking for guiding minimally invasive procedures

In a wide range of clinical procedures, accurate placement of medical devices such as needles and catheters is critical to optimize patient outcomes. Ultrasound imaging is often used to guide minimally invasive procedures, as it can provide real-time visualization of patient anatomy and medical devices. However, this modality can provide low image contrast for soft tissues, and poor visualization of medical devices that are steeply angled with respect to the incoming ultrasound beams. Photoacoustic sensors can provide information about the spatial distributions of tissue chromophores that could be valuable for guiding minimally invasive procedures. In this study, a system for guiding minimally invasive procedures using photoacoustic sensing was developed. This system included a miniature photoacoustic probe with three optical fibers: one with a bare end for photoacoustic excitation of tissue, a second for photoacoustic excitation of an optically absorbing coating at the distal end to transmit ultrasound, and a third with a Fabry-Perot cavity at the distal end for receiving ultrasound. The position of the photoacoustic probe was determined with ultrasonic tracking, which involved transmitting pulses from a linear-array ultrasound imaging probe at the tissue surface, and receiving them with the fiber-optic ultrasound receiver in the photoacoustic probe. The axial resolution of photoacoustic sensing was better than 70 μm, and the tracking accuracy was better than 1 mm in both axial and lateral dimensions. By translating the photoacoustic probe, depth scans were obtained from different spatial positions, and two-dimensional images were reconstructed using a frequency-domain algorithm.

Quantification of light attenuation in optically cleared mouse brains

Optical clearing, in combination with recently developed optical imaging techniques, enables visualization and acquisition of high-resolution, three-dimensional images of biological structures deep within the tissue. Many different approaches can be used to reduce light absorption and scattering within the tissue, but there is a paucity of research on the quantification of clearing efficacy. With the use of a custom-made spectroscopy system, we developed a way to quantify the quality of clearing in biological tissue and applied it to the mouse brain. Three clearing techniques were compared: BABB (1:2 mixture of benzyl alcohol and benzyl benzoate, also known as Murray’s clear), pBABB (peroxide BABB, a modification of BABB which includes the use of hydrogen peroxide), and passive CLARITY. We found that BABB and pBABB produced the highest degree of optical clearing. Furthermore, the approach allows regional measurement of light attenuation to be performed, and our results show that light is most attenuated in regions with high lipid content. We provide a way to choose between the multiple clearing protocols available, and it could prove useful for evaluating images that are acquired with cleared tissues.

Anatomically realistic ultrasound phantoms using gel wax with 3D printed moulds

Abstract Here we describe methods for creating tissue-mimicking ultrasound phantoms based on patient anatomy using a soft material called gel wax. To recreate acoustically realistic tissue properties, two additives to gel wax were considered: paraffin wax to increase acoustic attenuation, and solid glass spheres to increase backscattering. The frequency dependence of ultrasound attenuation was well described with a power law over the measured range of 3–10 MHz. With the addition of paraffin wax in concentrations of 0 to 8 w/w%, attenuation varied from 0.72 to 2.91 dB cm−1 at 3 MHz and from 6.84 to 26.63 dB cm−1 at 10 MHz. With solid glass sphere concentrations in the range of 0.025–0.9 w/w%, acoustic backscattering consistent with a wide range of ultrasonic appearances was achieved. Native gel wax maintained its integrity during compressive deformations up to 60%; its Young’s modulus was 17.4  ±  1.4 kPa. The gel wax with additives was shaped by melting and pouring it into 3D printed moulds. Three different phantoms were constructed: a nerve and vessel phantom for peripheral nerve blocks, a heart atrium phantom, and a placental phantom for minimally-invasive fetal interventions. In the first, nerves and vessels were represented as hyperechoic and hypoechoic tubular structures, respectively, in a homogeneous background. The second phantom comprised atria derived from an MRI scan of a patient with an intervening septum and adjoining vena cavae. The third comprised the chorionic surface of a placenta with superficial fetal vessels derived from an image of a post-partum human placenta. Gel wax is a material with widely tuneable ultrasound properties and mechanical characteristics that are well suited for creating patient-specific ultrasound phantoms in several clinical disciplines.

Interventional multi-spectral photoacoustic imaging in laparoscopic surgery

Laparoscopic procedures can be an attractive treatment option for liver resection, with a shortened hospital stay and reduced morbidity compared to open surgery. One of the central challenges of this technique is visualisation of concealed structures within the liver, particularly the vasculature and tumourous tissue. As photoacoustic (PA) imaging can provide contrast for haemoglobin in real time, it may be well suited to guiding laparoscopic procedures in order to avoid inadvertent trauma to vascular structures. In this study, a clinical laparoscopic ultrasound probe was used to receive ultrasound for PA imaging and to obtain co-registered B-mode ultrasound (US) images. Pulsed excitation light was delivered to the tissue via a fibre bundle in dark-field mode. Monte Carlo simulations were performed to optimise the light delivery geometry for imaging targets at depths of 1 cm, 2 cm and 3 cm, and 3D-printed mounts were used to position the fibre bundle relative to the transducer according to the simulation results. The performance of the photoacoustic laparoscope system was evaluated with phantoms and tissue models. The clinical potential of hybrid PA/US imaging to improve the guidance of laparoscopic surgery is discussed.

An interventional multispectral photoacoustic imaging platform for the guidance of minimally invasive procedures

Precise and efficient guidance of medical devices is of paramount importance for many minimally invasive procedures. These procedures include fetal interventions, tumor biopsies and treatments, central venous catheterisations and peripheral nerve blocks. Ultrasound imaging is commonly used for guidance, but it often provides insufficient contrast with which to identify soft tissue structures such as vessels, tumors, and nerves. In this study, a hybrid interventional imaging system that combines ultrasound imaging and multispectral photoacoustic imaging for guiding minimally invasive procedures was developed and characterized. The system provides both structural information from ultrasound imaging and molecular information from multispectral photoacoustic imaging. It uses a commercial linear-array ultrasound imaging probe as the ultrasound receiver, with a multimode optical fiber embedded in a needle to deliver pulsed excitation light to tissue. Co-registration of ultrasound and photoacoustic images is achieved with the use of the same ultrasound receiver for both modalities. Using tissue ex vivo, the system successfully discriminated deep-located fat tissue from the surrounding muscle tissue. The measured photoacoustic spectrum of the fat tissue had good agreement with the lipid spectrum in literature.