Dr. Guolan Lu Profile

Dr. Guolan Lu

Postdoc at Stanford Univ

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Author

Publications (23)

Proceedings Article | 13 March 2024 Presentation

Direct measurement trials: use of optically labeled therapeutic antibodies in human trials identifies novel barriers to delivery in intact human tumors

Eben Rosenthal, Guolan Lu, Gary Nolan

Proceedings Volume PC12821, PC1282103 (2024) https://doi.org/10.1117/12.3009461

KEYWORDS: Tumors, Therapeutic antibodies, Pharmacology, Tissues, Therapeutics, Testing and analysis, Resection, Proteins, Matrices, In vivo imaging

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Proceedings Article | 7 March 2021 Presentation

First-in-human fluorescence imaging-guided surgery and drug delivery in solid tumors

Guolan Lu

Proceedings Volume 11625, 116250Y (2021) https://doi.org/10.1117/12.2595597

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Proceedings Article | 4 March 2019 Presentation

fluorescence-guided surgery with panitumumab-IRDye800 and cetuximab-IRDye800 in glioblastoma patients (Conference Presentation)

Quan Zhou, Sarah Miller, Nynke van den Berg, Guolan Lu, Hannes Vogel, Romain Cayrol, Nicholas Oberhelman, Stefania Chirita, Stan van Keulen, Gerald Grant, Gordon Li, Eben Rosenthal

Proceedings Volume 10862, 108620Y (2019) https://doi.org/10.1117/12.2510366

KEYWORDS: Tumors, Luminescence, Tissues, Surgery, Brain, Magnesium, Near infrared, Receptors, Monoclonal antibodies, Tissue optics

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Introduction: Glioblastoma (GBM) is the most common and devastating primary brain tumor. The recurrence rate remains high with a median survival of 15 months. GBM’s infiltrative nature results in ill-defined margins that makes maximal tumor resection with minimal morbidity a challenge. Epidermal growth factor receptor (EGFR) is the most frequently amplified gene in GBM (35-45% of tumors) and is associated with overexpression in about 40-98% of cases, a characteristic of more aggressive phenotypes. We hypothesize that fluorescence labeled anti-EGFR monoclonal antibodies (mAb), panitumumab-IRDye800 (pan800) and cetuximab-IRDye800 (cet800), could be leveraged to enhance tumor contrast during surgical resection and improve patient outcome. Methods: 50mg fluorescently labeled corresponding study drugs, pan800 and cet800 respectively, were administered 1-2 days in glioblastoma patients with contrast enhancing (CE) tumors prior to surgery following 100 mg loading dose of unlabeled cetuximab or panitumumab. Near-infrared fluorescence imaging of tumor and histologically negative peri-tumoral tissue was performed intraoperatively and ex vivo. Fluorescence was measured as mean fluorescence intensity (MFI), and tumor-to-background ratios (TBRs) were calculated by comparing MFIs of tumor and histologically uninvolved tissue. Results: Despite heterogeneous drug uptake across all resected brain tissues, mean fluorescence intensity (MFI) correlated strongly (R^2=0.97) with tumor volume among histologically confirmed tumor tissues. The smallest detectable tumor size in a closed-field setting was 4.2 x 2.7 mm^2 (8.2 mg) for pan800 and 8.5 x 6.6 mm^2 (70mg) for cet800. Tumor tissues from pan800 infusion had significantly higher mean TBR (8.1 ± 4.6) than cet800 infused ones in intraoperative imaging (3.3 ± 2.7; P = 0.004). NIR fluorescence from both test drugs provided high contrast to identify as few as a cluster of (5 ± 1) tumor cells in macroscopic imaging of whole sections of paraffin embedded tissues. Sensitivity and specificity of MFI for viable tumor detection was calculated and fluorescence was found to be highly sensitive (64.4% for pan800, 73.0% for cet800) and specific (98.0% for pan800, 66.3% for cet800) for viable tumor tissue while normal peri-tumoral tissue showed minimal fluorescence. No related grade-2 adverse events were observed 30 days beyond the infusion of either study drugs. Conclusion: EGFR antibody based imaging for contrast-enhanced glioblastomas proved safe in human patients and specific intratumoral delivery of NIR fluorescence provided high optical contrast and resolution for intraoperative image-guided resection. Fully humanized panitumumab-IRDye800 demonstrated superior detection sensitivity and tumor specificity over the chimeric cetuximab-IRDye800.

Proceedings Article | 4 March 2019 Presentation

Reversible blood-brain barrier modulation enhances in vivo delivery of panitumumab-IRDye800 to high-grade glioma in cranial window model (Conference Presentation)

Quan Zhou, Christy Wilson, Hannes Vogel, Nutte Teraphongphom, Robert Ertsey, Pauline Chu, Guolan Lu, Nynke van den Berg, Stan van Keulen, Naoki Nishio, Gerald Grant, Eben Rosenthal

Proceedings Volume 10864, 1086402 (2019) https://doi.org/10.1117/12.2511180

KEYWORDS: Modulation, Cranial windows, Tumors, Blood brain barrier, In vivo imaging, Brain, Near infrared, Surgery, Proteins, Animal model studies

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Background: Pediatric High-grade gliomas (pHGGs) are the No.1 cause of cancer-related deaths in children with median survival of less than a year. pHGGs tend to be infiltrative and appear irregularly shaped with ill-defined borders difficult to be distinguished from surrounding normal brain tissue. As the extent of surgical resection predicts survival, precise tumor removal with more accurate margin delineation means better treatment outcome and less loss of vital functions. While EGFR is one of the most commonly amplified genes in pHGGs, its protein-level expression is not as well characterized as in adult HGGs. Previously, near-infrared (NIR) dye labeled epidermal growth factor receptor (EGFR) antibody has served as contrast agent in fluorescence-guided surgery of head and neck cancer. However, it must overcome the blood-brain barrier (BBB) for effective intratumoral delivery in the case of brain cancer. Therefore, the latest advancement in reversible BBB opening with tight junction protein modulation has the potential to enable the molecular targeted imaging guidance of pHGG resection. Aims: The current study aimed to improve intratumoral delivery of NIR fluorescent EGFR antibody via reversible BBB permeability enhancement with siRNA modulation of tight junction protein in an orthotopic xenograft animal model of high-grade glioma with EGFR overexpression. Furthermore, resected pHGGs were examined for EGFR expression in order to stratify patient subpopulation most likely to benefit from intraoperative molecular imaging strategy that targets EGFR. Methods: An orthotopic high-grade glioma xenograft model was established in 6-15 week old mice (n=3) by intracranial injection of 10^6 EGFR-overexpressing high-grade glioma cells (D270, 10ul) 3mm below the surface of brain. Subsequently, the exposed brain was covered with a glass plate secured to the skull with cyanoacrylate glue. siRNA was selected from those targeting conserved regions of the mouse claudin-5 cDNA sequence. 20μg of claudin-5 siRNA was injected intravenously via the tail vein in an in vivo-Jet-PEI solution (Polyplus Transfection) at a rate of 0.2 ml/sec 10 days post tumor implant. 0.1mL tetramethylrhodamine (250kDa) and various sized FITC-dextran (4.4-150kDa) solutions were injected intravenously to visualize blood vessels and assess extravasation distance through cranial window via 2-photo microscopy. Enhanced permeability of BBB was characterized by increase in KTrans on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in the tumor region. Mean fluorescence intensity at 800nm was measured through cranial window with an in vivo NIR imager (Pearl Impulse, LI-COR Biosciences) 0-72 hours following tail vein injection of 200ug panitumumab-IRDye800 (pan800). Immunohistochemical analysis of EGFR expression was performed on surgically resected de novo primary pHGG tumors, from seven GBM and three anaplastic ependymoma patients respectively. Results: The siRNA has shown a reversible 80% suppression of claudin-5 at 48-hrs post-injection that returned to normal levels at 72 hours. More than three-fold increase in penetration distance of 70kDa enhancing agent was observed in extravascular space and a 74% increase in intratumoral permeability was observed on DCE-MRI. Intratumoral delivery of fluorescent EGFR antibody (panitumumab-IRDye800) occurred at 6 hours and peaked at 48 hours post systemic injection following BBB opening. Positive EGFR expression was found in 70% of all surgically removed high-grade pediatric brain tumor samples. The median age of patients with positive EGFR expression was 15 (IQR = 12.75 to 16.50), significantly higher (P = 0.018) than that of EGFR negative patients (median = 0.75, IQR = 0.47 to 5.38). Conclusions: We provided proof-of-concept evidence that the enabling technology of transient BBB modulation and fluorescence-guided imaging with EGFR targeting antibody has great potential for clinical translation to improve surgery outcome by providing tumor-specific precision resection to a significant subpopulation of young patients with pHGGs

Proceedings Article | 4 March 2019 Presentation

Predicting antibody penetration in a first-in-human clinical trial of head and neck cancers (Conference Presentation)

Guolan Lu, Shayan Fakurnejad, Brock Martin, Ashley Zhu, Nynke van den Berg, Stan van Keulen, Quan Zhou, Tarn Teraphongphom, Rebecca Gao, Nicholas Oberhelman, Stefania Chirita, Robert Erstey, Christina Kong, Dimitrios Colevas, Eben Rosenthal

Proceedings Volume 10859, 1085905 (2019) https://doi.org/10.1117/12.2513258

KEYWORDS: Tumors, Clinical trials, Head, Neck, Cancer, Image analysis, Tissues, Lymphatic system, Magnesium, Solids

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Proceedings Article | 14 March 2018 Presentation

Panitumumab-IRDye800 for fluorescence-guidance based metastatic lymph node identification in patients with head and neck cancer (Conference Presentation)

Nynke van den Berg, Nutte Teraphongphom, Willemieke S. F. Tummers, Steven Hong, Guolan Lu, Adam Gomez , Brock Martin, Robert Ertsey, Nicholas Oberhelman, Christina Kong, Dimitros Colevas, Eben Rosenthal

Proceedings Volume 10478, 104780T (2018) https://doi.org/10.1117/12.2291298

KEYWORDS: Tumors, Luminescence, Lymphatic system, Head, Neck, Cancer, Surgery, Imaging systems, Receptors

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Proceedings Article | 14 March 2018 Presentation

Handheld dual-modality wide-field fluorescent imaging guided dual-axis confocal microscope for fluorescence molecular guidance of precise tumor resection in head and neck surgery (Conference Presentation)

Zhen Qiu, Tarn Teraphongphom, Nynke van den Berg, Nathan Loewke, Guolan Lu, Robert Ertsey, Frank Schonig, Stephan Rogalla, Shai Friedland, Michael Mandella, Eben Rosenthal, Christopher Contag

Proceedings Volume 10478, 104780E (2018) https://doi.org/10.1117/12.2291986

KEYWORDS: Luminescence, Tissues, Microscopes, Tissue optics, Confocal microscopy, Tumors, Head, Neck, Imaging systems, Surgery

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SPIE Journal Paper | 28 August 2017 Open Access

Label-free reflectance hyperspectral imaging for tumor margin assessment: a pilot study on surgical specimens of cancer patients

Baowei Fei, Guolan Lu, Xu Wang, Hongzheng Zhang, James Little, Mihir Patel, Christopher Griffith, Mark El-Diery, Amy Chen

JBO, Vol. 22, Issue 08, 086009, (August 2017) https://doi.org/10.1117/12.10.1117/1.JBO.22.8.086009

KEYWORDS: Cancer, Tissues, Tumors, Hyperspectral imaging, Surgery, Reflectivity, Luminescence, Tissue optics, Image classification, Pathology

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SPIE Journal Paper | 24 June 2017 Open Access

Deep convolutional neural networks for classifying head and neck cancer using hyperspectral imaging

Martin Halicek, Guolan Lu, James Little, Xu Wang, Mihir Patel, Christopher C. Griffith, Mark El-Deiry, Amy Chen, Baowei Fei

JBO, Vol. 22, Issue 06, 060503, (June 2017) https://doi.org/10.1117/12.10.1117/1.JBO.22.6.060503

KEYWORDS: Cancer, Head, Neck, Hyperspectral imaging, Convolutional neural networks, Tissues, Optical properties, Tissue optics

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Proceedings Article | 13 March 2017 Paper

Deep learning based classification for head and neck cancer detection with hyperspectral imaging in an animal model

Ling Ma, Guolan Lu, Dongsheng Wang, Xu Wang, Zhuo Georgia Chen, Susan Muller, Amy Chen, Baowei Fei

Proceedings Volume 10137, 101372G (2017) https://doi.org/10.1117/12.2255562

KEYWORDS: Convolutional neural networks, Hyperspectral imaging, Head, Neck, Cancer, Animal model studies, Neural networks, Image-guided intervention, Data acquisition, Tumors, Image classification

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Proceedings Article | 14 February 2017 Paper

Tumor margin assessment of surgical tissue specimen of cancer patients using label-free hyperspectral imaging

Baowei Fei, Guolan Lu, Xu Wang, Hongzheng Zhang, James Little, Kelly Magliocca, Amy Chen

Proceedings Volume 10054, 100540E (2017) https://doi.org/10.1117/12.2249803

KEYWORDS: Machine learning, Tissues, Hyperspectral imaging, Image-guided intervention, Head, Neck, Cancer, Image classification, Biomedical optics, Diagnostics, Tumors, Surgery, Luminescence, Tissue optics

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Proceedings Article | 29 March 2016 Paper

Hyperspectral imaging of neoplastic progression in a mouse model of oral carcinogenesis

Guolan Lu, Xulei Qin, Dongsheng Wang, Susan Muller, Hongzheng Zhang, Amy Chen, Zhuo Georgia Chen, Baowei Fei

Proceedings Volume 9788, 978812 (2016) https://doi.org/10.1117/12.2216553

KEYWORDS: Cancer, Hyperspectral imaging, Image classification, Optical imaging, Mouse models, Image quality, Tongue, Tissues, Tumor growth modeling, Detection and tracking algorithms, Tumors, Reflectivity, Pathology, RGB color model, Image segmentation

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Proceedings Article | 29 March 2016 Paper

Superpixel-based spectral classification for the detection of head and neck cancer with hyperspectral imaging

Hyunkoo Chung, Guolan Lu, Zhiqiang Tian, Dongsheng Wang, Zhuo Georgia Chen, Baowei Fei

Proceedings Volume 9788, 978813 (2016) https://doi.org/10.1117/12.2216559

KEYWORDS: Hyperspectral imaging, Cancer, Head, Neck, Image classification, Research management, Feature extraction, Information technology, Tissues, Optical imaging, Tumors, Image segmentation, Principal component analysis, Imaging systems, Green fluorescent protein

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Proceedings Article | 23 March 2016 Paper

Quantitative diagnosis of tongue cancer from histological images in an animal model

Guolan Lu, Xulei Qin, Dongsheng Wang, Susan Muller, Hongzheng Zhang, Amy Chen, Zhuo Chen, Baowei Fei

Proceedings Volume 9791, 97910L (2016) https://doi.org/10.1117/12.2217286

KEYWORDS: Image segmentation, Cancer, Tissues, Tongue, RGB color model, Tumor growth modeling, Feature extraction, Tumors, Animal model studies, Solid modeling

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SPIE Journal Paper | 28 December 2015 Open Access

Framework for hyperspectral image processing and quantification for cancer detection during animal tumor surgery

Guolan Lu, Dongsheng Wang, Xulei Qin, Luma Halig, Susan Muller, Hongzheng Zhang, Amy Chen, Brian Pogue, Zhuo Chen, Baowei Fei

JBO, Vol. 20, Issue 12, 126012, (December 2015) https://doi.org/10.1117/12.10.1117/1.JBO.20.12.126012

KEYWORDS: Tumors, Tissues, Cancer, Hyperspectral imaging, Surgery, Reflectivity, Feature extraction, Green fluorescent protein, Visualization, Image classification

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Proceedings Article | 18 March 2015 Paper

Quantitative wavelength analysis and image classification for intraoperative cancer diagnosis with hyperspectral imaging

Guolan Lu, Xulei Qin, Dongsheng Wang, Zhuo Georgia Chen, Baowei Fei

Proceedings Volume 9415, 94151B (2015) https://doi.org/10.1117/12.2082284

KEYWORDS: Tumors, Tissues, Cancer, Hyperspectral imaging, Reflectivity, Surgery, Image classification, Green fluorescent protein, RGB color model, Image segmentation

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Proceedings Article | 17 March 2015 Paper

Estimation of tissue optical parameters with hyperspectral imaging and spectral unmixing

Guolan Lu, Xulei Qin, Dongsheng Wang, Zhuo Chen, Baowei Fei

Proceedings Volume 9417, 94170Q (2015) https://doi.org/10.1117/12.2082299

KEYWORDS: Hyperspectral imaging, Cancer, Tissue optics, Tumors, Absorption, Oxygen, Tissues, Chromophores, In vivo imaging, Blood vessels

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SPIE Journal Paper | 2 October 2014 Open Access

Spectral-spatial classification for noninvasive cancer detection using hyperspectral imaging

Guolan Lu, Luma Halig, Dongsheng Wang, Xulei Qin, Zhuo Georgia Chen, Baowei Fei

JBO, Vol. 19, Issue 10, 106004, (October 2014) https://doi.org/10.1117/12.10.1117/1.JBO.19.10.106004

KEYWORDS: Tumors, Tissues, Reflectivity, Hyperspectral imaging, Cancer, Green fluorescent protein, Image classification, Tissue optics, RGB color model, In vivo imaging

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Proceedings Article | 21 March 2014 Paper

A minimum spanning forest based hyperspectral image classification method for cancerous tissue detection

Robert Pike, Samuel Patton, Guolan Lu, Luma Halig, Dongsheng Wang, Zhuo Georgia Chen, Baowei Fei

Proceedings Volume 9034, 90341W (2014) https://doi.org/10.1117/12.2043848

KEYWORDS: Tissues, Hyperspectral imaging, Image classification, Tumors, Image segmentation, Cancer, Luminescence, Green fluorescent protein, Gold, Library classification systems

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Proceedings Article | 21 March 2014 Paper

Spectral-spatial classification using tensor modeling for cancer detection with hyperspectral imaging

Guolan Lu, Luma Halig, Dongsheng Wang, Zhuo Georgia Chen, Baowei Fei

Proceedings Volume 9034, 903413 (2014) https://doi.org/10.1117/12.2043796

KEYWORDS: Tumors, Cancer, Hyperspectral imaging, Tissues, Tumor growth modeling, Head, Neck, Performance modeling, Image classification, Green fluorescent protein

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Proceedings Article | 21 March 2014 Paper

Breast tissue classification in digital tomosynthesis images based on global gradient minimization and texture features

Xulei Qin, Guolan Lu, Ioannis Sechopoulos, Baowei Fei

Proceedings Volume 9034, 90341V (2014) https://doi.org/10.1117/12.2043828

KEYWORDS: Tissues, Digital breast tomosynthesis, Image filtering, Image classification, Breast, Image segmentation, Mammography, Gold, Image processing, Fuzzy logic

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Proceedings Article | 12 March 2014 Paper

Hyperspectral imaging for cancer surgical margin delineation: registration of hyperspectral and histological images

Guolan Lu, Luma Halig, Dongsheng Wang, Zhuo Chen, Baowei Fei

Proceedings Volume 9036, 90360S (2014) https://doi.org/10.1117/12.2043805

KEYWORDS: Tumors, Image registration, Hyperspectral imaging, Cancer, Tissues, Principal component analysis, In vivo imaging, Head, Surgery, Green fluorescent protein

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SPIE Journal Paper | 20 January 2014 Open Access

Medical hyperspectral imaging: a review

Guolan Lu, Baowei Fei

JBO, Vol. 19, Issue 01, 010901, (January 2014) https://doi.org/10.1117/12.10.1117/1.JBO.19.1.010901

KEYWORDS: Tissues, Tissue optics, Reflectivity, Hyperspectral imaging, Luminescence, Surgery, Charge-coupled devices, Tumors, Imaging systems, Cancer

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