Master of Engineering, Cornell University (2007)
Master of Science, Cornell University (2013)
Doctor of Philosophy, Cornell University (2014)
C Xu, WW Webb, DS Scherr, DG Ouzounov, DR Rivera, CM. Brown, D Kobat, D Huland, SS Howard.. "United States Patent 20120140301 Multi-path, multi-magnification, non-confocal fluorescence emission endoscopy apparatus and methods.", Cornell University, Apr 22, 2014
Current Research and Scholarly Interests
Clinical translation of novel optical techniques to improve on current cancer diagnostic and therapeutic methods.
Sanjiv Gambhir, (12/7/2015)
Intraoperative Pancreatic Cancer Detection using Tumor-Specific Multimodality Molecular Imaging.
Annals of surgical oncology
2018; 25 (7): 1880–88
BACKGROUND: Operative management of pancreatic ductal adenocarcinoma (PDAC) is complicated by several key decisions during the procedure. Identification of metastatic disease at the outset and, when none is found, complete (R0) resection of primary tumor are key to optimizing clinical outcomes. The use of tumor-targeted molecular imaging, based on photoacoustic and fluorescence optical imaging, can provide crucial information to the surgeon. The first-in-human use of multimodality molecular imaging for intraoperative detection of pancreatic cancer is reported using cetuximab-IRDye800, a near-infrared fluorescent agent that binds to epidermal growth factor receptor.METHODS: A dose-escalation study was performed to assess safety and feasibility of targeting and identifying PDAC in a tumor-specific manner using cetuximab-IRDye800 in patients undergoing surgical resection for pancreatic cancer. Patients received a loading dose of 100mg of unlabeled cetuximab before infusion of cetuximab-IRDye800 (50mg or 100mg). Multi-instrument fluorescence imaging was performed throughout the surgery in addition to fluorescence and photoacoustic imaging ex vivo.RESULTS: Seven patients with resectable pancreatic masses suspected to be PDAC were enrolled in this study. Fluorescence imaging successfully identified tumor with a significantly higher mean fluorescence intensity in the tumor (0.09±0.06) versus surrounding normal pancreatic tissue (0.02±0.01), and pancreatitis (0.04±0.01; p<0.001), with a sensitivity of 96.1% and specificity of 67.0%. The mean photoacoustic signal in the tumor site was 3.7-fold higher than surrounding tissue.CONCLUSIONS: The safety and feasibilty of intraoperative, tumor-specific detection of PDAC using cetuximab-IRDye800 with multimodal molecular imaging of the primary tumor and metastases was demonstrated.
View details for DOI 10.1245/s10434-018-6453-2
View details for PubMedID 29667116
Multiphoton gradient index endoscopy for evaluation of diseased human prostatic tissue ex vivo
JOURNAL OF BIOMEDICAL OPTICS
2014; 19 (11)
Multiphoton microscopy can instantly visualize cellular details in unstained tissues. Multiphoton probes with clinical potential have been developed. This study evaluates the suitability of multiphoton gradient index (GRIN) endoscopy as a diagnostic tool for prostatic tissue. A portable and compact multiphoton endoscope based on a 1-mm diameter, 8-cm length GRIN lens system probe was used. Fresh ex vivo samples were obtained from 14 radical prostatectomy patients and benign and malignant areas were imaged and correlated with subsequent H&E sections. Multiphoton GRIN endoscopy images of unfixed and unprocessed prostate tissue at a subcellular resolution are presented. We note several differences and identifying features of benign versus low-grade versus high-grade tumors and are able to identify periprostatic tissues such as adipocytes, periprostatic nerves, and blood vessels. Multiphoton GRIN endoscopy can be used to identify both benign and malignant lesions in ex vivo human prostate tissue and may be a valuable diagnostic tool for real-time visualization of suspicious areas of the prostate.
View details for DOI 10.1117/1.JBO.19.11.116011
View details for Web of Science ID 000347442000034
View details for PubMedID 25415446
View details for PubMedCentralID PMC4409031
- Intravital Multiphoton Endoscopy Advances in Intravital Microscopy edited by Weigert, R. Springer. 2014
Multiphoton microscopy: applications in Urology and Andrology.
Translational andrology and urology
2014; 3 (1): 77–83
Multiphoton microscopy (MPM) enables real-time imaging of various cellular processes at submicron resolution. MPM is currently being used in neuroscience, oncology, and immunology. MPM has demonstrated promising results in urology. MPM has been used in the identification of spermatogenesis, evaluation of bladder cancer, and tissue identification in prostate cancer surgery. MPM has allowed the visualization of seminiferous tubules within the testis in a rat model and identified areas of spermatogenesis. MPM could potentially improve the efficacy of testicular sperm extraction. In bladder cancer evaluation, MPM has proven to be an effective imaging tool in identifying areas suspicious for malignancy. The imaging technology could be utilized in the future to provide urologists with an immediate impression of extracted bladder tissue, or as part of a cystoscopic device to evaluate the bladder in real time. Similarly, MPM has proven to be a useful imaging technique to evaluate prostate cancer. MPM could be utilized during a prostatectomy to help differentiate prostate from cavernous nerves that are closely adherent to the prostate. MPM uses a laser and safety studies will need to be performed prior to its utilization in the clinical setting.
View details for DOI 10.3978/j.issn.2223-4683.2014.01.01
View details for PubMedID 25741460
View details for PubMedCentralID PMC4345420
Three-photon excited fluorescence imaging of unstained tissue using a GRIN lens endoscope
BIOMEDICAL OPTICS EXPRESS
2013; 4 (5): 652-658
We present a compact and portable three-photon gradient index (GRIN) lens endoscope system suitable for imaging of unstained tissues, potentially deep within the body, using a GRIN lens system of 1 mm diameter and 8 cm length. The lateral and axial resolution in water is 1.0 μm and 9.5 μm, respectively. The ~200 μm diameter field of view is imaged at 2 frames/s using a fiber-based excitation source at 1040 nm. Ex vivo imaging is demonstrated with unstained mouse lung at 5.9 mW average power. These results demonstrate the feasibility of three-photon GRIN lens endoscopy for optical biopsy.
View details for DOI 10.1364/BOE.4.000652
View details for Web of Science ID 000318421400001
View details for PubMedID 23667782
View details for PubMedCentralID PMC3646593
In vivo imaging of unstained tissues using long gradient index lens multiphoton endoscopic systems
BIOMEDICAL OPTICS EXPRESS
2012; 3 (5): 1077-1085
We characterize long (up to 285 mm) gradient index (GRIN) lens endoscope systems for multiphoton imaging. We fabricate a portable, rigid endoscope system suitable for imaging unstained tissues, potentially deep within the body, using a GRIN lens system of 1 mm diameter and 8 cm length. The portable device is capable of imaging a ~200 µm diameter field of view at 4 frames/s. The lateral and axial resolution in water is 0.85 µm and 7.4 µm respectively. In vivo images of unstained tissues in live, anesthetized rats using the portable device are presented. These results show great promise for GRIN endoscopy to be used clinically.
View details for Web of Science ID 000303537400021
View details for PubMedID 22567597
View details for PubMedCentralID PMC3342183
Identification of Spermatogenesis With Multiphoton Microscopy: An Evaluation in a Rodent Model
JOURNAL OF UROLOGY
2011; 186 (6): 2487-2492
Microdissection testicular sperm extraction has replaced conventional testis biopsies for men with nonobstructive azoospermia and it has become first line treatment. The current problem is that the decision to retrieve tubules is based only on appearance and there is no guarantee that the tubules removed contain sperm. Multiphoton microscopy enables label-free immediate visualization of many biological processes in living tissue at subcellular resolution.We used multiphoton microscopy to study the different developmental stages of spermatogenesis using neonatal, pubertal and adult rat testes. We used a testis hypothermia plus ischemia model to study different testicular histopathologies with multiphoton microscopy. To assess the risk of photo damage DNA fragmentation in testis biopsies imaged at different intensities was assessed by TUNEL assay.Multiphoton microscopy identified the stage of spermatogenesis in a seminiferous tubule in fresh tissue without using exogenous labels. We noted significant differences in fluorescence and spectroscopic characteristics between tubules with and without sperm. Sertoli's-cell only tubules had abundant autofluorescence in the 420 to 490 and 550 to 650 nm wavelength ranges while tubules containing sperm had autofluorescence only in the 420 to 490 nm range. On DNA fragmentation assay sperm from tubules imaged by multiphoton microscopy had minimal DNA fragmentation at the laser intensities needed to distinguish tubules with and without sperm.Multiphoton microscopy has the potential to facilitate real-time visualization of spermatogenesis in humans and aid in clinical applications, such as testicular sperm extraction for men with infertility.
View details for DOI 10.1016/j.juro.2011.07.081
View details for Web of Science ID 000296758600109
View details for PubMedID 22019169
Sub-Surface, Micrometer-Scale Incisions Produced in Rodent Cortex using Tightly-Focused Femtosecond Laser Pulses
LASERS IN SURGERY AND MEDICINE
2011; 43 (5): 382-391
Techniques that allow targeted, micrometer-scale disruption in the depths of biological tissue, without affecting overlying structures or causing significant collateral damage, could potentially lead to new surgical procedures. We describe an optical technique to make sub-surface incisions in in vivo rodent brain and characterize the relationship between the cut width and maximum depth of these optical transections as a function of laser energy.To produce cuts, high intensity, femtosecond laser pulses were tightly focused into and translated within the cortex, through a craniotomy, in anesthetized rodents. Imaging of stained brain slices was used to characterize cut width and maximum cutting depth.Cut width decreased exponentially as a function of depth and increased as the cube root of laser energy, but showed about 50% variation at fixed depth and laser energy. For example, at a laser energy of 13 µJ, cut width decreased from 158 ± 43.1 µm (mean ± standard deviation) to 56 ± 33 µm over depths of approximately 200-800 µm, respectively. Maximal cut depth increased logarithmically with laser energy, with cut depths of up to 1 mm achieved with 13 µJ pulses. We further showcased this technique by selectively cutting sub-surface cortical dendrites in a live, anesthetized transgenic mouse.Femtosecond laser pulses provide the novel capacity for precise, sub-surface, cellular-scale cuts for surgical applications in optically scattering tissues.
View details for DOI 10.1002/lsm.21054
View details for Web of Science ID 000292470000004
View details for PubMedID 21674543