Dr. Xu Cao Profile

Dr. Xu Cao

at Thayer School of Engineering at Dartmouth

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Author

Publications (18)

SPIE Journal Paper | 20 April 2023 Open Access

Stable tissue-mimicking phantoms for longitudinal multimodality imaging studies that incorporate optical, CT, and MRI contrast

Mengyang Zhao, Mingwei Zhou, Xu Cao, Jinchao Feng, Brian W. Pogue, Keith D. Paulsen, Shudong Jiang

JBO, Vol. 28, Issue 04, 046006, (April 2023) https://doi.org/10.1117/12.10.1117/1.JBO.28.4.046006

KEYWORDS: Pigments, Optical properties, Magnetic resonance imaging, Multimodal imaging, Tissues, X-ray computed tomography, Computed tomography, Breast, Soft tissue optics, Near infrared

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Proceedings Article | 15 March 2023 Presentation + Paper

Automated motion artifact correction for dynamic contrast-enhanced fluorescence imaging during open orthopedic surgery

Yue Tang, I. Leah Gitajn, Xu Cao, Xinyue Han, Jonathan Elliott, Xiaohan Yu, Logan Bateman, Bethany Malskis, Lillian Fisher, Jessica Sin, Eric Henderson, Brian Pogue, Shudong Jiang

Proceedings Volume 12361, 1236104 (2023) https://doi.org/10.1117/12.2650028

KEYWORDS: Bone, Surgery, Fluorescence imaging, Biological imaging, Perfusion imaging, Targeting Task Performance metric, Indocyanine green, Data acquisition, Orthopedic imaging, Bone imaging

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Proceedings Article | 6 March 2023 Presentation + Paper

MRI-guided near-infrared spectroscopic tomographic system for breast cancer imaging: phantom and normal-subject studies

Mengyang Zhao, Xu Cao, Mingwei Zhou, Jinchao Feng, Luxi Xia, Brian Pogue, Keith Paulsen, Shudong Jiang

Proceedings Volume 12371, 1237104 (2023) https://doi.org/10.1117/12.2647571

KEYWORDS: Magnetic resonance imaging, Imaging systems, Interfaces, Signal detection, Data acquisition, Breast cancer, Tomography, Imaging spectroscopy, Multimodal imaging, Near infrared spectroscopy

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Proceedings Article | 4 March 2022 Presentation + Paper

Dynamic contrast-enhanced fluorescence imaging compared with MR imaging in evaluating bone perfusion during open orthopedic surgery

Yue Tang, Jessica Sin, I. Leah Gitajn, Xu Cao, Xinyue Han, Jonathan Elliott, Xiaohan Yu, Melanie Christian, Logan Bateman, Theresa Chockbengboun, Eric Henderson, Brian Pogue, Shudong Jiang

Proceedings Volume 11943, 119430C (2022) https://doi.org/10.1117/12.2608382

KEYWORDS: Magnetic resonance imaging, Bone, Surgery, Software development, Data modeling, Indocyanine green, Orthopedic imaging, Bone imaging

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Proceedings Article | 2 March 2022 Poster + Paper

MRI-guided near-infrared spectroscopic tomography (MRg-NIRST): system development for wearable, simultaneous NIRS and MRI imaging

Mengyang Zhao, Xu Cao, Mingwei Zhou, Jinchao Feng, Luxi Xia, Brian Pogue, Keith Paulsen, Shudong Jiang

Proceedings Volume 11952, 119520E (2022) https://doi.org/10.1117/12.2607983

KEYWORDS: Breast cancer, Multimodal imaging, Tomography, Magnetic resonance imaging, Optical fibers, Data acquisition, Imaging systems, Interfaces, Near infrared spectroscopy

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SPIE Journal Paper | 13 October 2021 Open Access

Optimization of in vivo Cherenkov imaging dosimetry via spectral choices for ambient background lights and filtering

Mahbubur Rahman, Petr Bruza, Rachael Hachadorian, Daniel Alexander, Xu Cao, Rongxiao Zhang, David Gladstone, Brian Pogue

JBO, Vol. 26, Issue 10, 106003, (October 2021) https://doi.org/10.1117/12.10.1117/1.JBO.26.10.106003

KEYWORDS: Light sources, Optical filters, Signal to noise ratio, Light, Image filtering, In vivo imaging, Tissue optics, Image quality, Light emitting diodes, Cameras

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Significance: The Cherenkov emission spectrum overlaps with that of ambient room light sources. Choice of room lighting devices dramatically affects the efficient detection of Cherenkov emission during patient treatment. Aim: To determine optimal room light sources allowing Cherenkov emission imaging in normally lit radiotherapy treatment delivery rooms. Approach: A variety of commercial light sources and long-pass (LP) filters were surveyed for spectral band separation from the red to near-infrared Cherenkov light emitted by tissue. Their effects on signal-to-noise ratio (SNR), Cherenkov to background signal ratio, and image artifacts were quantified by imaging irradiated tissue equivalent phantoms with an intensified time-gated CMOS camera. Results: Because Cherenkov emission from tissue lies largely in the near-infrared spectrum, a controlled choice of ambient light that avoids this spectral band is ideal, along with a camera that is maximally sensitive to it. An RGB LED light source produced the best SNR out of all sources that mimic room light temperature. A 675-nm LP filter on the camera input further reduced ambient light detected (optical density > 3), achieving maximal SNR for Cherenkov emission near 40. Reduction of the room light signal reduced artifacts from specular reflection on the tissue surface and also minimized spurious Cherenkov signals from non-tissue features such as bolus. Conclusions: LP filtering during image acquisition for near-infrared light in tandem with narrow band LED illuminated rooms improves image quality, trading off the loss of red wavelengths for better removal of room light in the image. This spectral filtering is also critically important to remove specular reflection in the images and allow for imaging of Cherenkov emission through clear bolus. Beyond time-gated external beam therapy systems, the spectral separation methods can be utilized for background removal for continuous treatment delivery methods including proton pencil beam scanning systems and brachytherapy.

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Proceedings Article | 5 March 2021 Paper

ICG-based dynamic contrast-enhanced fluorescence imaging guided open orthopaedic surgery: pilot patient study

Shudong Jiang, Jonathan Elliott, Jin Xing, Xu Cao, Xiaohan Yu, Xinyue Han, Rebecca Dabrowski, Melanie Christian, Eric Henderson, Brian Pogue, I. Leah Gitajn

Proceedings Volume 11625, 116250W (2021) https://doi.org/10.1117/12.2578976

KEYWORDS: Bone, Luminescence, Tissues, Blood circulation, Surgery, Machine learning, Indocyanine green, Contamination

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Proceedings Article | 5 March 2021 Presentation + Paper

MRI guided wearable near infrared spectral tomography: simulation study

Jinchao Feng, Chengpu Wei, Shudong Jiang, Mingwei Zhou, Xu Cao, Brian Pogue, Keith Paulsen

Proceedings Volume 11639, 116390D (2021) https://doi.org/10.1117/12.2578356

KEYWORDS: Magnetic resonance imaging, Breast, Tomography, Near infrared, Sensors, Tumors, Sensing systems, Nipple, Near infrared spectroscopy, Light

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Proceedings Article | 5 March 2021 Poster + Paper

MRI-guide near infrared spectroscopic tomographic imaging system with wearable optical breast interface for breast imaging

Shudong Jiang, Xu Cao, Mingwei Zhou, Jinchao Feng, Brian Pogue, Keith Paulsen

Proceedings Volume 11639, 116391J (2021) https://doi.org/10.1117/12.2579087

KEYWORDS: Breast, Magnetic resonance imaging, Tomography, Spectroscopy, Near infrared spectroscopy, Near infrared, Interfaces, Imaging spectroscopy, Light, Imaging systems

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SPIE Journal Paper | 1 January 2021 Open Access

Review of in vivo optical molecular imaging and sensing from x-ray excitation

Brian Pogue, Rongxiao Zhang, Xu Cao, Mengyu Jia, Arthur Petusseau, Petr Bruza, Sergei Vinogradov

JBO, Vol. 26, Issue 01, 010902, (January 2021) https://doi.org/10.1117/12.10.1117/1.JBO.26.1.010902

KEYWORDS: X-rays, Tissue optics, X-ray imaging, X-ray optics, Luminescence, In vivo imaging, Tissues, Molecular imaging, Signal detection, X-ray sources

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Significance: Deep-tissue penetration by x-rays to induce optical responses of specific molecular reporters is a new way to sense and image features of tissue function in vivo. Advances in this field are emerging, as biocompatible probes are invented along with innovations in how to optimally utilize x-ray sources. Aim: A comprehensive review is provided of the many tools and techniques developed for x-ray-induced optical molecular sensing, covering topics ranging from foundations of x-ray fluorescence imaging and x-ray tomography to the adaptation of these methods for sensing and imaging in vivo. Approach: The ways in which x-rays can interact with molecules and lead to their optical luminescence are reviewed, including temporal methods based on gated acquisition and multipoint scanning for improved lateral or axial resolution. Results: While some known probes can generate light upon x-ray scintillation, there has been an emergent recognition that excitation of molecular probes by x-ray-induced Cherenkov light is also possible. Emission of Cherenkov radiation requires a threshold energy of x-rays in the high kV or MV range, but has the advantage of being able to excite a broad range of optical molecular probes. In comparison, most scintillating agents are more readily activated by lower keV x-ray energies but are composed of crystalline inorganic constituents, although some organic biocompatible agents have been designed as well. Methods to create high-resolution structured x-ray-optical images are now available, based upon unique scanning approaches and/or a priori knowledge of the scanned x-ray beam geometry. Further improvements in spatial resolution can be achieved by careful system design and algorithm optimization. Current applications of these hybrid x-ray-optical approaches include imaging of tissue oxygenation and pH as well as of certain fluorescent proteins. Conclusions: Discovery of x-ray-excited reporters combined with optimized x-ray scan sequences can improve imaging resolution and sensitivity.

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SPIE Journal Paper | 24 November 2020 Open Access

Implantable sensor for local Cherenkov-excited luminescence imaging of tumor pO₂ during radiotherapy

Xu Cao, Jason Gunn, Srinivasa Rao Allu, Petr Bruza, Shudong Jiang, Sergei Vinogradov, Brian Pogue

JBO, Vol. 25, Issue 11, 112704, (November 2020) https://doi.org/10.1117/12.10.1117/1.JBO.25.11.112704

KEYWORDS: Oxygen, Tumors, Sensors, Tissues, Radiotherapy, Phosphorescence, Luminescence, Toxicity, Positron emission tomography, Image sensors

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Significance: The necessity to use exogenous probes for optical oxygen measurements in radiotherapy poses challenges for clinical applications. Options for implantable probe biotechnology need to be improved to alleviate toxicity concerns in human use and facilitate translation to clinical trial use. Aim: To develop an implantable oxygen sensor containing a phosphorescent oxygen probe such that the overall administered dose of the probe would be below the Federal Drug Administration (FDA)-prescribed microdose level, and the sensor would provide local high-intensity signal for longitudinal measurements of tissue pO2. Approach: PtG4, an oxygen quenched dendritic molecule, was mixed into an agarose matrix at 100 μM concentration, allowing for local injection into tumors at the total dose of 10 nmol per animal, forming a gel at the site of injection. Cherenkov-excited luminescence imaging (CELI) was used to acquire the phosphorescence and provide intratumoral pO2. Results: Although PtG4 does not form covalent bonds with agarose and gradually leaches out into the surrounding tissue, its retention time within the gel was sufficiently long to demonstrate the capability to measure intratumoral pO2 with the implantable gel sensors. The sensor’s performance was first evaluated in vitro in tissue simulation phantoms, and then the sensor was used to measure changes in oxygen in MDA-MB-231 tumors during hypofractionated radiotherapy. Conclusions: Our study demonstrates that implantable oxygen sensors in combination with CELI present a promising approach for quantifying oxygen changes during the course of radiation therapy and thus for evaluating the tumor response to radiation. By improving the design of the gel–probe composition in order to prevent leaching of the probe into the tissue, biosensors can be created that should allow longitudinal oxygen measurements in tumors by means of CELI while using FDA-compliant microdose levels of the probe and thus lowering toxicity concerns.

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Proceedings Article | 14 August 2019 Presentation

High resolution imaging of tumor pO2 with Cherenkov-excited luminescence scanned imaging (Conference Presentation)

Brian Pogue, Ethan LaRochelle, Xu Cao, Jason Gunn, Jennifer Shell, Cuiping Yao, Sergei Vinogradov

Proceedings Volume 11070, 110705E (2019) https://doi.org/10.1117/12.2525602

KEYWORDS: Tumors, Luminescence, Image resolution, Oxygen, Tissues, Tissue optics, Diagnostics, Molecules, Sensors, In vivo imaging

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Proceedings Article | 8 April 2019 Paper

Pharmacokinetic biodistribution assessment of Phosphorescent sensor, PtG4 Oxyphor in mice for optimization of in vivo oxygenation imaging

Mengyu Jia, Jennifer Shell, Xu Cao, Jason Gunn, Sergei Vinogradov, Brian Pogue

Proceedings Volume 10862, 108621H (2019) https://doi.org/10.1117/12.2513220

KEYWORDS: Cerenkov radiation imaging, In vivo imaging, Tumors, Luminescence, Medicine, Imaging systems

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SPIE Journal Paper | 8 March 2019 Open Access

Characterizing short-wave infrared fluorescence of conventional near-infrared fluorophores

Brook K. Byrd, Margaret R. Folaron, Joseph P. Leonor, Rendall R. Strawbridge, Xu Cao, Petr Brůža, Scott C. Davis

JBO, Vol. 24, Issue 03, 035004, (March 2019) https://doi.org/10.1117/12.10.1117/1.JBO.24.3.035004

KEYWORDS: Short wave infrared radiation, Luminescence, Infrared radiation, Imaging systems, Infrared imaging, Fluorescence spectroscopy, Spectroscopy, Biomedical optics, Tissue optics, Cameras

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Proceedings Article | 7 March 2019 Presentation + Paper

Tomographic Cherenkov-excited luminescence scanned imaging based on back-projection reconstruction demonstrates 0.3mm spatial resolution for molecular reporter through 2-3cm of tissue

Mengyu Jia, Xu Cao, Jason Gunn, Petr Bruza, Shudong Jiang, Brian Pogue

Proceedings Volume 10862, 108621A (2019) https://doi.org/10.1117/12.2513231

KEYWORDS: Luminescence, X-rays, Tomography, Signal to noise ratio, Tissues, Radiotherapy, Photons, Image restoration, Spatial resolution, Computed tomography

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Cherenkov-excited luminescence scanned imaging (CELSI) is achieved with External Beam Radiotherapy, to map out molecular luminescence intensity or lifetime in tissue. In order to realize a deeper imaging depth with a reasonable spatial resolution, we optimized the original scanning gesture to do in a similar way to computed tomography (CT) and the image reconstruction was instead used a customized Maximum-likelihood expectation maximization (ML-EM) for CELSI. In tomographic CELSI (TCELSI), tomographic images are generated by irradiating the subject using a sequence of programmed X-ray beams at a fixed projection angle, while sensitive measurement is to take a sum for all image pixels from an intensified charge-coupled device. By restricting the X-ray excitation to a single, narrow beam of radiation, the origin of the optical photons can be inferred regardless of where these photons were detected, and how many times they scattered in tissue. Measurement geometry was designed for clinical expectation: CT scanning was achieved by a clinical linear accelerator (LINAC), where X-ray beam sequence and multiple projections were realized with multi leaf collimator (MLC) and gantry movement, respectively. Furthermore, in most modern External Beam Radiotherapy, MLC movement is synchronized with gantry angle to release a uniform radiation, and some of treatment plans, e.g., Intensity Modulated Radiation Therapy (IMRT), have a potential to match the scanning way mentioned. By including Cherenkov imaging results, medium surface profile can be additionally acquired, which can be used as boundary reference to do depth correction and co-register with molecular images. Resolution phantom studies showed that a 0.3 mm diameter capillary tube containing 0.01 nM luminescent nanospheres could be recognized at a depth of 21 mm into tissue-like media. Small animal imaging with a 1 mm diameter cylindrical target demonstrated that fast 3D data acquisition was achieved by a multi-pinhole collimator to image local luminescence 20mm deep.

Proceedings Article | 4 March 2019 Presentation

Advancing optical methods for real-time non-contact pO2 estimation during external beam radiation therapy (Conference Presentation)

Ethan Philip LaRochelle, Jennifer Shell, Mengyu Jia, Xu Cao, Petr Bruza, Sergei Vinogradov, Brian Pogue

Proceedings Volume 10862, 108621E (2019) https://doi.org/10.1117/12.2511292

KEYWORDS: Radiotherapy, Beam analyzers, Tumors, Oxygen, Solids, Hypoxia, Tissue optics, In vivo imaging, Environmental sensing, Imaging devices

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Proceedings Article | 4 March 2019 Presentation

Tumor targeting cetuximab conjugated europium microspheres for Cherenkov excited luminescence scanned imaging (Conference Presentation)

Jennifer Shell, Liberty Gendron, Ethan LaRochelle, Xu Cao, Brian Pogue

Proceedings Volume 10862, 1086217 (2019) https://doi.org/10.1117/12.2515383

KEYWORDS: Tumors, Luminescence, Europium, Radiotherapy, Phototherapy, In vitro testing, Microscopy, Visualization, In vivo imaging

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SPIE Journal Paper | 22 November 2018 Open Access

Cherenkov excited short-wavelength infrared fluorescence imaging in vivo with external beam radiation

Xu Cao, Shudong Jiang, Mengyu Jeremy Jia, Jason Gunn, Tianshun Miao, Scott Davis, Petr Bruza, Brian Pogue

JBO, Vol. 24, Issue 05, 051405, (November 2018) https://doi.org/10.1117/12.10.1117/1.JBO.24.5.051405

KEYWORDS: Short wave infrared radiation, Luminescence, Cameras, In vivo imaging, Infrared imaging, Infrared radiation, Electron beams, Tissues, Radiotherapy, Absorption

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