multimodal-3d-printing-of-phantoms-to-simulate-biological-tissue

Multimodal 3D Printing of Phantoms to Simulate Biological Tissue

Biomedical optical imaging is playing an important role in diagnosis and treatment of various diseases. However, the accuracy and the reproducibility of ...

University of Science and Technology of China

A wearable surgical navigation system is developed for intraoperative imaging of surgical margin in cancer resection surgery. The system consists of an excitation light source, a monochromatic CCD camera, a host computer, and a wearable headset unit in either of the following two modes: head-mounted display (HMD) and Google glass. In the HMD mode, a CMOS camera is installed on a personal cinema system to capture the surgical scene in real-time and transmit the image to the host computer through a USB port. In the Google glass mode, a wireless connection is established between the glass and the host computer for image acquisition and data transport tasks. A software program is written in Python to call OpenCV functions for image calibration, co-registration, fusion, and display with augmented reality. The imaging performance of the surgical navigation system is characterized in a tumor simulating phantom. Image-guided surgical resection is demonstrated in an ex vivo tissue model. Surgical margins identified by the wearable navigation system are co-incident with those acquired by a standard small animal imaging system, indicating the technical feasibility for intraoperative surgical margin detection. The proposed surgical navigation system combines the sensitivity and specificity of a fluorescence imaging system and the mobility of a wearable goggle. It can be potentially used by a surgeon to identify the residual tumor foci and reduce the risk of recurrent diseases without interfering with the regular resection procedure. 

Designing a wearable navigation system for image-guided cancer resection surgery.

Author's reply to the reader's comment on "designing a wearable navigation system for image-guided cancer resection surgery".

Biomedical optical devices are widely used for clinical detection of various tissue anomalies. However, optical measurements have limited accuracy and traceability, partially owing to the lack of effective calibration methods that simulate the actual tissue conditions. To facilitate standardized calibration and performance evaluation of medical optical devices, we develop a three-dimensional fuse deposition modeling (FDM) technique for freeform fabrication of tissue-simulating phantoms. The FDM system uses transparent gel wax as the base material, titanium dioxide (TiO2 ) powder as the scattering ingredient, and graphite powder as the absorption ingredient. The ingredients are preheated, mixed, and deposited at the designated ratios layer-by-layer to simulate tissue structural and optical heterogeneities. By printing the sections of human brain model based on magnetic resonance images, we demonstrate the capability for simulating tissue structural heterogeneities. By measuring optical properties of multilayered phantoms and comparing with numerical simulation, we demonstrate the feasibility for simulating tissue optical properties. By creating a rat head phantom with embedded vasculature, we demonstrate the potential for mimicking physiologic processes of a living system.

Three-dimensional fuse deposition modeling of tissue-simulating phantom for biomedical optical imaging.

Surgical resection remains the primary curative treatment for many early-stage cancers, including breast cancer. The development of intraoperative guidance systems for identifying all sites of disease and improving the likelihood of complete surgical resection is an area of active ongoing research, as this can lead to a decrease in the need of subsequent additional surgical procedures. We develop a wearable goggle navigation system for dual-mode optical and ultrasound imaging of suspicious lesions. The system consists of a light source module, a monochromatic CCD camera, an ultrasound system, a Google Glass, and a host computer. It is tested in tissue-simulating phantoms and an ex vivo human breast tissue model. Our experiments demonstrate that the surgical navigation system provides useful guidance for localization and core needle biopsy of simulated tumor within the tissue-simulating phantom, as well as a core needle biopsy and subsequent excision of Indocyanine Green (ICG)-fluorescing sentinel lymph nodes. Our experiments support the contention that this wearable goggle navigation system can be potentially very useful and fully integrated by the surgeon for optimizing many aspects of oncologic surgery. Further engineering optimization and additional in vivo clinical validation work is necessary before such a surgical navigation system can be fully realized in the everyday clinical setting. 

A Wearable Goggle Navigation System for Dual-Mode Optical and Ultrasound Localization of Suspicious Lesions: Validation Studies Using Tissue-Simulating Phantoms and an Ex Vivo Human Breast Tissue Model.

We propose a projective navigation system for fluorescence imaging and image display in a natural mode of visual perception. The system consists of an excitation light source, a monochromatic charge coupled device (CCD) camera, a host computer, a projector, a proximity sensor and a Complementary metal-oxide-semiconductor (CMOS) camera. With perspective transformation and calibration, our surgical navigation system is able to achieve an overall imaging speed higher than 60 frames per second, with a latency of 330 ms, a spatial sensitivity better than 0.5 mm in both vertical and horizontal directions, and a projection bias less than 1 mm. The technical feasibility of image-guided surgery is demonstrated in both agar-agar gel phantoms and an ex vivo chicken breast model embedding Indocyanine Green (ICG). The biological utility of the system is demonstrated in vivo in a classic model of ICG hepatic metabolism. Our benchtop, ex vivo and in vivo experiments demonstrate the clinical potential for intraoperative delineation of disease margin and image-guided resection surgery. 

Benchtop and Animal Validation of a Projective Imaging System for Potential Use in Intraoperative Surgical Guidance.

Current flow-based blood counting devices require expensive and centralized medical infrastructure and are not appropriate for field use. In this article we report a streamlined, easy-to-use method to count red blood cells (RBC), white blood cells (WBC), platelets (PLT) and 3-part WBC differential through a cost-effective and automated image-based blood counting system. The approach consists of using a compact, custom-built microscope with large field-of-view to record bright-field and fluorescence images of samples that are diluted with a single, stable reagent mixture and counted using automatic algorithms. Sample collection utilizes volume-controlled capillary tubes, which are then dropped into a premixed, shelf-stable solution to stain and dilute in a single step. Sample measurement and analysis are fully automated, requiring no input from the user. Cost of the system is minimized through the use of custom-designed motorized components. We compare the performance of our system, as operated by trained and untrained users, to the clinical gold standard on 120 adult blood samples, demonstrating agreement within Clinical Laboratory Improvement Amendments guidelines, with no statistical difference in performance among different operator groups. The system's cost-effectiveness, automation and performance indicate that it can be successfully translated for use in low-resource settings where central hematology laboratories are not accessible.

Performance of a cost-effective and automated blood counting system for resource-limited settings operated by trained and untrained users.

We propose a portable fluorescence microscopic imaging system (PFMS) for intraoperative display of biliary structure and prevention of iatrogenic injuries during cholecystectomy. The system consists of a light source module, a camera module, and a Raspberry Pi computer with an LCD. Indocyanine green (ICG) is used as a fluorescent contrast agent for experimental validation of the system. Fluorescence intensities of the ICG aqueous solution at different concentration levels are acquired by our PFMS and compared with those of a commercial Xenogen IVIS system. We study the fluorescence detection depth by superposing different thicknesses of chicken breast on an ICG-loaded agar phantom. We verify the technical feasibility for identifying potential iatrogenic injury in cholecystectomy using a rat model in vivo. The proposed PFMS system is portable, inexpensive, and suitable for deployment in resource-limited settings.

Benchtop and animal validation of a portable fluorescence microscopic imaging system for potential use in cholecystectomy.

Phantoms simulating polarization characteristics of soft tissue play an important role in the development, calibration, and validation of diagnostic polarized imaging devices and of therapeutic strategy, in both laboratory and clinical settings. We propose to fabricate optical phantoms that simulate polarization characteristics of dense fibrous tissues by bonding electrospun polylactic acid (PLA) fibers between polydimethylsiloxane (PDMS) substrate with a groove. Increasing the rotational speed of an electrospinning collector helps improve the orientation of the electrospun fibers. The phantoms simulate the polarization characteristics of dense fibrous tissue of collagenous fibroma and healthy skin with high fidelity. Our experiments demonstrate the technical potential of using such phantoms for validation and calibration of polarimetric medical devices.

Simulating orientation and polarization characteristics of dense fibrous tissue by electrostatic spinning of polymeric fibers.

We propose a handheld projective imaging device for orthotopic projection of near-infrared fluorescence images onto target biological tissue at visible wavelengths without any additional visual aid. The device integrates a laser diode light source module, a camera module, a projector, an ultrasonic distance sensor, a Raspberry Pi single-board computer, and a battery module in a rugged handheld unit. It is calibrated at the detected working distance for seamless coregistration between fluorescence emission and projective imaging at the target tissue site. The proposed device is able to achieve a projection resolution higher than 314  μm and a planar projection bias less than 1 mm at a projection field of view of 58  ×  108  mm2 and a working distance of 27 cm. Technical feasibility for projective imaging is verified in an ex vivo model of chicken breast tissue using indocyanine green as a fluorescence agent. Clinical utility for image-guided surgery is demonstrated in a clinical trial where sentinel lymph nodes in breast cancer patients are identified and resected under the guidance of projective imaging. Our ex vivo and in vivo experiments imply the clinical utility of deploying the proposed device for image-guided surgical interventions in resource-limited settings.

Handheld projective imaging device for near-infrared fluorescence imaging and intraoperative guidance of sentinel lymph node resection.

A coaxial projective imaging (CPI) module acquires surgical scene images from the local site of surgery, transfers them wirelessly to the remote site, and projects instructive annotations to the surgical field. At the remote site, the surgical scene images are displayed, and the instructive annotations from a surgical specialist are wirelessly transferred back to the local site in order to guide the surgical intervention by a less experienced surgeon. The CPI module achieves seamless imaging of the surgical field and accurate projection of the instructive annotations, by a coaxial optical path design that couples the imaging arm with the projection arm and by a color correction algorithm that recovers the true color of the surgical scene. Our benchtop study of tele-guided intervention verifies that the proposed system has a positional accuracy of better than 1 mm at a working distance ranging from 300 to 500 mm. Our in vivo study of cricothyrotomy in a rabbit model proves the concept of tele-mentored surgical navigation. This is the first report of tele-guided surgery based on CPI. The proposed technique can be potentially used for surgical training and for telementored surgery in resource-limited settings.

Article	Year
Designing a wearable navigation system for image-guided cancer resection surgery. Annals of biomedical engineering\| PubMed ID: 24980159	2014
Author's reply to the reader's comment on "designing a wearable navigation system for image-guided cancer resection surgery". Annals of biomedical engineering\| PubMed ID: 25323571	2014
Three-dimensional fuse deposition modeling of tissue-simulating phantom for biomedical optical imaging. Journal of biomedical optics\| PubMed ID: 26603611	2015
A Wearable Goggle Navigation System for Dual-Mode Optical and Ultrasound Localization of Suspicious Lesions: Validation Studies Using Tissue-Simulating Phantoms and an Ex Vivo Human Breast T... PloS one\| PubMed ID: 27367051	2016
Benchtop and Animal Validation of a Projective Imaging System for Potential Use in Intraoperative Surgical Guidance. PloS one\| PubMed ID: 27391764	2016
Performance of a cost-effective and automated blood counting system for resource-limited settings operated by trained and untrained users. Journal of biophotonics\| PubMed ID: 28688219	2018
Benchtop and animal validation of a portable fluorescence microscopic imaging system for potential use in cholecystectomy. Journal of biomedical optics\| PubMed ID: 29473349	2018
Simulating orientation and polarization characteristics of dense fibrous tissue by electrostatic spinning of polymeric fibers. Biomedical optics express\| PubMed ID: 30800500	2019
Handheld projective imaging device for near-infrared fluorescence imaging and intraoperative guidance of sentinel lymph node resection. Journal of biomedical optics\| PubMed ID: 31436070	2019
Coaxial projective imaging system for surgical navigation and telementoring. Journal of biomedical optics\| PubMed ID: 31650743	2019

Pengfei Shao

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