About

Kai Chen is an Assistant Professor of Chemistry at the University of Pennsylvania. His research focuses on several interdisciplinary areas including Biological Chemistry, Biomolecular Engineering, Biophysical Chemistry, Chemical Biology, Nanoscale Science and Engineering, and Organic Chemistry. He is based in room 3003 of the Institute for Advanced Science and Technology (IAST). The information provided highlights his broad expertise across multiple cutting-edge fields within chemistry, emphasizing his engagement with both the biological and physical aspects of chemical sciences as well as nanoscale and organic chemistry. No additional biographical or research detail is provided in the text.

Research topics

• Medicine
• Immunology
• Biology
• Pathology

Selected publications

• Comparing spatial distributions of ALA-PpIX and indocyanine green in a whole pig brain glioma model using 3D fluorescence cryotomography

  Journal of Biomedical Optics · 2024-09-06 · 5 citations

  articleOpen access

  Significance: ALA-PpIX and second-window indocyanine green (ICG) have been studied widely for guiding the resection of high-grade gliomas. These agents have different mechanisms of action and uptake characteristics, which can affect their performance as surgical guidance agents. Elucidating these differences in animal models that approach the size and anatomy of the human brain would help guide the use of these agents. Herein, we report on the use of a new pig glioma model and fluorescence cryotomography to evaluate the 3D distributions of both agents throughout the whole brain. Aim: We aim to assess and compare the 3D spatial distributions of ALA-PpIX and second-window ICG in a glioma-bearing pig brain using fluorescence cryotomography. Approach: A glioma was induced in the brain of a transgenic Oncopig via adeno-associated virus delivery of Cre-recombinase plasmids. After tumor induction, the pro-drug 5-ALA and ICG were administered to the animal 3 and 24 h prior to brain harvest, respectively. The harvested brain was imaged using fluorescence cryotomography. The fluorescence distributions of both agents were evaluated in 3D in the whole brain using various spatial distribution and contrast performance metrics. Results: Significant differences in the spatial distributions of both agents were observed. Indocyanine green accumulated within the tumor core, whereas ALA-PpIX appeared more toward the tumor periphery. Both ALA-PpIX and second-window ICG provided elevated tumor-to-background contrast (13 and 23, respectively). Conclusions: This study is the first to demonstrate the use of a new glioma model and large-specimen fluorescence cryotomography to evaluate and compare imaging agent distribution at high resolution in 3D.

  PublisherDOI

• Evaluation of multiple fluorescent agents and intraoperative MRI in a novel pig glioma model for fluorescence guided neurosurgery

  2024-01-26

  article

  Pre-operative MRI with gadolinium-based contrast agents (Gd-MRI) is a central feature in surgical planning and intra-surgical navigation of glioma, yet brain movement during the surgical procedure can degrade the accuracy of these pre-operative images. Fluorescence guided neurosurgery is a technique which can complement MRI guidance by providing direct visualization of the tumor during surgery, and several agents either used routinely or under clinical development have shown effective tumor discrimination and impact on surgical outcomes. We have built a multi-spectral kinetic imaging system to acquire behavior of fluorophores overtime in animal models. Here, we exhibit this fluorescence kinetic imaging system and report its performance with tissue-simulating phantoms with multiple fluorophores. Also reported is our first experience with multiple fluorescent contrast agents in a novel oncopig model.

  PublisherDOI

• Recent Advances in Juvenile Dermatomyositis: Moving toward Integration of Myositis-Specific Antibody Clinical Phenotypes, IFN-Driven Pathogenesis, and Targeted Therapies

  Journal of Investigative Dermatology · 2024-11-12 · 1 citations

  review1st authorCorresponding
  PublisherDOI

• Comparing fluorescent contrast agents for fluorescence guided surgery using 3-D cryo-imaging

  2024-03-13

  articleOpen access

  Fluorescence cryo-imaging is a high-resolution optical imaging technique that produces 3-D whole-body biodistributions of fluorescent molecules within an animal specimen. To accomplish this, animal specimens are administered a fluorescent molecule or reporter and are frozen to be autonomously sectioned and imaged at a temperature of -20°C or below. Thus, to apply this technique effectively, administered fluorescent molecules should be relatively invariant to low temperature conditions for cryo-imaging and ideally the fluorescence intensity should be stable and consistent in both physiological and cryo-imaging conditions. Herein, we assessed the mean fluorescence intensity of 11 fluorescent contrast agents as they are frozen in a tissue-simulating phantom experiment and show an example of a tested fluorescent contrast agent in a cryo-imaged whole pig brain. Most fluorescent contrast agents were stable within ~25% except for FITC and PEGylated FITC derivatives, which showed a dramatic decrease in fluorescence intensity when frozen.

  PublisherOA PDFDOI

• Intraoperative stereovision cortical surface segmentation using fast segment anything model

  2024-03-29 · 3 citations

  article

  <strong>Introduction</strong> In image-guided open cranial surgeries, brain deformation may compromise the accuracy of image guidance immediately following the opening of the dura. A biomechanical model has been developed to update pre-operative MR images to match intraoperative stereovision (iSV), and maintain the accuracy of image guidance. Current methods necessitate manual segmentation of the cortical surface from iSV, a process that demands expertise and prolongs computational time . <strong>Methods </strong>In this study, we adopted the Fast Segment Anything Model (FastSAM), a newly developed deep learning model that automatically can segment the cortical surface from iSV after dural opening without customized training. We evaluated its performance against manual segmentation as well as a U-Net model. In one patient case, FastSAM was applied to segment the cortical surface with an automatic box prompt, and the segmentation was used for image updating. We compared the three cortical surface segmentation methods in terms of segmentation accuracy (Dice Similarity Coefficient; DSC) and image updating accuracy (target registration errors; TRE). <strong>Results</strong> All three segmentation methods demonstrated high DSC (&gt;0.95). FastSAM and manual segmentation produced similar performance in terms of image updating efficiency and TRE (~2.2 mm). <strong>Conclusion</strong> In summary, the performance of FastSAM was consistent with manual segmentation in terms of segmentation accuracy and image updating accuracy. The results suggest FastSAM can be employed in the image updating process to replace manual segmentation to improve efficiency and reduce user dependency.

  PublisherDOI

• Therapeutic effect of NEO400, perillyl alcohol conjugated to linoleic acid, in a mouse model of UV‐induced skin damage

  Photochemistry and Photobiology · 2024-07-05 · 1 citations

  articleOpen access

  Excessive exposure to ultraviolet radiation (UVR) causes harmful effects on human skin. Pre-exposure application of sunscreen can be protective, but not after damage already has occurred. There is a need for agents that can be applied post-UVR exposure to repair the damage. We investigated a novel compound, NEO400, that appears to meet this medicinal need. NEO400 was created by conjugating linoleic acid to perillyl alcohol. UVR was repeatedly administered to the skin of mice over several weeks, where it caused the typical signs of UV damage, including scaling of the skin, DNA damage, and elevated levels of inflammatory cytokines. However, when NEO400 was applied immediately post-UVR, it triggered the appearance of markers for dermal stem cell proliferation, and no signs of skin damage emerged. Furthermore, when NEO400 was applied to skin that already had incurred significant damage, it accelerated skin healing. When applied individually, linoleic acid and perillyl alcohol were ineffective, indicating that they had to be conjugated in order to exert therapeutic efficacy. None of these skin-protective effects could be achieved with Aloe vera gel, a popular and widely used post-exposure remedy. Our study suggests that NEO400 holds potential as a regenerative treatment for excessively UVR-exposed skin.

  PublisherOA PDFDOI

• Novel method to improve feature extraction in MR for model-based image updating in image-guided neurosurgery

  2024-02-16 · 1 citations

  article1st authorCorresponding

  In image-guided neurosurgery, preoperative magnetic resonance (pMR) images are rigidly registered with the patient’s head in the operating room. Image-guided systems incorporate this spatial information to provide real-time information on where surgical instruments are located with respect to preoperative imaging. The accuracy of these systems rely on the rigid relationship between the patient’s brain and the preoperative scan, which typically does not hold true due to intraoperative brain shift. To account for this brain shift, we previously developed an image-guidance updating framework that incorporates brain shift information acquired from registering intraoperative stereovision (iSV) surface with the pMR surface to create an updated magnetic resonance image (uMR). To register the iSV surface and the pMR surface, the two surfaces must have some matching features that can be used for registration. However, for some cases, the matching features could fall outside of the segmented brain volume causing a lack of matching features for registration between iSV and pMR surfaces. To capture features falling outside of the brain volume, we have developed a method to improve feature extraction, which involves performing a selective dilation in the region of the stereovision surface. The goal of this method is to capture features that fall outside of the brain volume without capturing too much noise. With further testing, this method has potential in supplementing brain segmentation to improve image registration between iSV and pMR surfaces within the image-guidance updating framework.

  PublisherDOI

• Porcine-human glioma xenograft model. Immunosuppression and model reproducibility

  Cancer Treatment and Research Communications · 2024-01-01 · 5 citations

  articleOpen access

  BACKGROUND: Glioblastoma is the most common primary malignant and treatment-resistant human brain tumor. Rodent models have played an important role in understanding brain cancer biology and treatment. However, due to their small cranium and tumor volume mismatch, relative to human disease, they have been less useful for translational studies. Therefore, development of a consistent and simple large animal glioma xenograft model would have significant translational benefits. METHODS: ) were stereotactically implanted into the left frontal cortex. The implanted brains were imaged by MRI for monitoring. In a separate study, tumors were grown in 5 additional pigs using the combined regimen, and pigs underwent tumor resection with intra-operative image updating to determine if the xenograft model could accurately capture the spatial tumor resection challenges seen in humans. RESULTS: Tumors were successfully implanted and grown in 11 pigs. One animal in cyclosporine only group failed to show clinical tumor growth. Clinical tumor growth, assessed by MRI, progressed slowly over the first 10 days, then rapidly over the next 10 days. The average tumor growth latency period was 20 days. Animals were monitored twice daily and detailed records were kept throughout the experimental period. Pigs were sacrificed humanely when the tumor reached 1 - 2 cm. Some pigs experienced decreased appetite and activity, however none required premature euthanasia. In the image updating study, all five pigs demonstrated brain shift after craniotomy, consistent with what is observed in humans. Intraoperative image updating was able to accurately capture and correct for this shift in all five pigs. CONCLUSION: This report demonstrates the development and use of a human intracranial glioma model in an immunosuppressed, but nongenetically modified pig. While the immunosuppression of the model may limit its utility in certain studies, the model does overcome several limitations of small animal or genetically modified models. For instance, we demonstrate use of this model for guiding surgical resection with intraoperative image-updating technologies. We further report use of a surrogate extracranial tumor that indicates growth of the intracranial tumor, allowing for relative growth assessment without radiological imaging.

  PublisherDOI

• Smart line detection and histogram-based approach to robust freehand ultrasound calibration

  2024-02-16

  article

  Tracked intraoperative ultrasound (iUS) is growing in use. Accurate spatial calibration is essential to enable iUS navigation. Utilizing sterilizable probes introduces new challenges that can be solved by time-of-surgery calibration that is robust, efficient and user independent performed within the sterile field. This study demonstrates a smart line detection scheme to perform calibration based on video acquisition data and investigates the effect of pose variation on the accuracy of a plane-based calibration. A user-independent US video is collected of a calibration phantom and a smart line detection and tracking filter applied to the video-tracking data pairs to remove poor calibration candidates. A localized point target phantom is imaged to provide a TRE assessment of the calibration. The tracking data is decoupled into 6 degrees of freedom and these ranges iteratively reduced to study the effect on the spatial calibration accuracy in order to indicate the sufficient amount of pose variation required during video acquisition to maintain high TRE accuracy. This work facilitates a larger development toward user-independent, video based iUS calibration at the time of surgery.

  PublisherDOI

• Towards accounting for intraoperative spine motion: a simulation study of registration between stereovision surfaces

  2023-04-03 · 2 citations

  articleOpen access

  Registration of preoperative or intraoperative imaging is necessary to facilitate surgical navigation in spine surgery. After image acquisition, intervertebral motion and spine pose changes can occur during surgery from instrumentation, decompression, physician manipulation or correction. This causes deviations from the reference imaging reducing the navigation accuracy. To evaluate the ability to use the registration between stereovision surfaces in order to account for this intraoperative spine motion through a simulation study. Co-registered CT and stereovision surface data were obtained of a swine cadaver’s exposed lumbar spine in the prone position. Data was segmented and labeled by vertebral level. A simulation of biomechanically bounded motion was applied to each vertebral level to move the prone spine to a new position. A reduced surface data set was then registered level-wise back to the prone spines original position. The average surface to surface distance was recorded between simulated and prone positions. Localized targets on these surfaces were used for a calculation of target registration error. Target registration error increases with distance between surfaces. Movement exceeding 2.43 cm between stereovision acquisitions exceeds registration accuracy of 2mm. Lateral bending of the spine contributes most to this effect compared to axial rotation and flexion-extension. In conclusion, the viability of using stereovision-to-stereovision registration to account for interoperative motion of the spine is shown through this simulation. It is suggested the distance of spine movement between corresponding points does not surpass 2.43 cm between stereovision acquisitions.

  PublisherOA PDFDOI

Frequent coauthors

• Victoria P. Werth

  Philadelphia VA Medical Center

  37 shared

• Majid Zeidi

  United States Department of Veterans Affairs

  30 shared

• Keith D. Paulsen

  26 shared

• Xiaoyao Fan

  Dartmouth College

  13 shared

• Muhammad M. Bashir

  University of Pennsylvania

  12 shared

• Basil Patel

  University of Florida

  12 shared

• Jay Patel

  12 shared

• Rachel Lim

  Providence College

  10 shared

Education

• Ph.D., Chemical Biology

  University of California, Berkeley

Awards & honors

• Caltech Herbert Newby McCoy Award (2020)
• Caltech Milton and Francis Clauser Doctoral Prize (2020)
• Life Science Research Foundation (LSRF) Postdoctoral Fellows…
• Rett Syndrome Research Trust (RSRT) Award (2025)