About

Hao Zhang is a Professor of Biomedical Engineering at Northwestern University, based in the McCormick School of Engineering. His research interests include optical coherence tomography, single-molecular imaging, ophthalmology, vision science, and genomics. He has contributed to the development and application of advanced optical imaging techniques, particularly in the context of vision and ophthalmology, with a focus on high-speed, high-resolution imaging modalities such as visible-light optical coherence tomography and spectroscopic microscopy. His work aims to connect innovative optical methods with clinical and biological applications, advancing understanding in vision science and related fields.

Research topics

• Ophthalmology
• Medicine
• Computer Science
• Biology
• Physics
• Neuroscience
• Bioinformatics
• Optics
• Anatomy
• Endocrinology

Selected publications

• Super-resolution functional photoacoustic microscopy via label-free cell tracking

  Light Science & Applications · 2026-03-03 · 1 citations

  articleOpen access

  Microvascular function and oxygen metabolism are central to tissue and organ health. However, label-free methods for imaging oxygen dynamics in three-dimensional (3D) microvascular networks at the level of single red blood cells (RBCs)-the fundamental units of oxygen transport in vivo-remain lacking. Here, we introduce super-resolution functional photoacoustic microscopy (SR-fPAM), which spatiotemporally tracks RBC movements under dual-wavelength excitation. SR-fPAM reconstructs super-resolved 3D microvascular architecture comparable to two-photon microscopy while providing quantitative measurements of RBC flow and oxygenation. In live mice, SR-fPAM revealed redistribution of oxygen and hemodynamics across 3D microvascular networks following a single-vessel stroke. These findings establish SR-fPAM as an enabling tool that bridges a critical gap in oxygen-metabolism imaging and opens new avenues for studying microvascular health and disease with unprecedented functional insights.

  PublisherOA PDFDOI

• JoVE Video Dataset

  2026-03-07

  database

  Super-resolution imaging has revolutionized biological research by revealing structural details at the nanoscale. Most optical super-resolution methods rely on fluorescent labeling of biomolecules, which enables specific tagging of molecular species but can disrupt cellular functions, introduce inaccuracies from linker molecules, and fail to provide the consistent high labeling density required for chromatin imaging at the scale of individual DNA molecules. A technology that enables label-free, in situ genomic imaging with nanometer resolution would profoundly impact biology. Here, we present a protocol that harnesses the intrinsic fluorescence of DNA to perform spectroscopic single-molecule localization microscopy (sSMLM). The protocol details sample preparation, data acquisition, and spectral analysis. Briefly, a thin DNA gel is created by depositing a polynucleotide solution onto glass and allowing it to dry for hours. After gel formation, the sample is imaged in the presence of an imaging buffer using sSMLM. The recorded dataset comprises a zeroth-order image, providing spatial localizations, and a first-order image, encoding the emission spectrum of each localization. Spatial reconstructions are generated from the zeroth-order data, after which the corresponding spectra are extracted from the first-order signal. Finally, we demonstrate the feasibility of this approach using multiple excitation wavelengths and DNA molecules with varying lengths, sequences, and compositions.

  PublisherDOI

• Quantifying the spatial distribution of post-translational histone modifications using 3D spectroscopic single-molecule localization microscopy

  2025-03-19

  articleSenior author

  Super-resolution microscopy has enabled studies that probe protein spatial distribution at the nanoscale. This, in turn, has made it possible to study the distribution of post-translational modifications in the nucleus. Cancer is associated with widespread alterations in gene expression. It is of interest to classify the resulting change in the spatial distribution of post-translational modifications. However, there is a lack of studies that examine the interactions of multiple histone modifications in a single nucleus. We quantified the individual distribution and clustering behaviors of H3K27me3 and H3K27ac and classified the level of contact between these histone modifications using spectroscopic single-molecule localization microscopy (sSMLM). We also associated the detected changes in these parameters with degrees of cancer malignancy and with drug-induced perturbations in methylation machinery.

  PublisherDOI

• Integrated visible-light optical coherence tomography and fluorescence scanning laser ophthalmoscopy to image retinal ganglion cell axons

  Biomedical Optics Express · 2025-06-13 · 3 citations

  articleOpen accessSenior author

  Retinal ganglion cell (RGC) soma and axonal damage is a hallmark of optic neuropathies. Visible-light OCT fibergraphy (vis-OCTF) enables non-invasive imaging and quantitative assessment of individual RGC axon bundles; however, validating vis-OCTF using confocal fluorescence imaging of flat-mounted postmortem retina is less accurate due to structural alterations caused by flat-mount preparation and cannot be performed longitudinally. For in vivo vis-OCTF validation, we developed an integrated visible-light optical coherence tomography (vis-OCT) and fluorescence scanning laser ophthalmoscopy (SLO) system. The vis-OCT had a 100 nm bandwidth with a center wavelength of 560 nm, offering an axial resolution of 1.3 µm in the retina. The lateral resolutions of vis-OCT and SLO were 4 µm and 3.5 µm, respectively. In the transgenic Eno2-YFP mice, we showed that vis-OCTF and SLO provide consistent RGC axon bundle imaging results. Measuring 30 axon bundle widths from six mice yielded a Pearson correlation coefficient of 0.991 between SLO and vis-OCTF. Thus, the combined SLO and vis-OCT can potentially achieve multimodal longitudinal in vivo studies of RGC pathologies.

  PublisherDOI

• Peripartum aortic dissection: a rare case of Stanford type B dissection triggered by severe labor pain

  The Egyptian Heart Journal · 2025-11-16

  articleOpen accessSenior author

  BACKGROUND: Peripartum aortic dissection (AD) is an uncommon yet significant complication during pregnancy and delivery, characterized by a tear in the aortic intima that can lead to severe maternal morbidity and mortality. This case report describes a rare instance of Stanford Type B aortic dissection occurring in a pregnant woman, emphasizing that acute, severe labor pain can obscure the diagnosis of AD, often leading to misattribution of symptoms to more common obstetric complications. CASE PRESENTATION: This report highlights the case of a 36-year-old primigravida who presented with acute chest pain during labor, initially misdiagnosed until imaging revealed the dissection post-delivery. The critical interplay between labor-induced hemodynamic stress and pre-existing vascular weaknesses, such as those found in connective tissue disorders, raises concerns about the cardiovascular risks faced by pregnant individuals. The importance of a multidisciplinary approach, involving obstetricians, cardiologists, and anesthesiologists, is underscored, as effective management strategies are essential to ensure maternal and fetal safety. CONCLUSION: This case underscores the necessity for healthcare providers to maintain a high index of suspicion for atypical thoracic pain in pregnant patients and advocates for enhanced screening protocols for aortic disease. The findings advocate for regular cardiovascular assessments in women of childbearing age with known risk factors to improve early diagnosis and intervention, thereby potentially reducing the associated morbidity and mortality from this rare but critical condition. Further research is needed to develop evidence-based guidelines for managing AD in the peripartum setting, aiming to refine clinical protocols and optimize patient outcomes.

  PublisherOA PDFDOI

• Production and Use of Customizable Agarose Molds for Scaffold-Free Mouse Ovarian Follicle Culture

  Journal of Visualized Experiments · 2025-10-24 · 2 citations

  articleOpen access

  The ovarian follicle is the functional unit of the ovary that produces hormones and gametes needed to sustain female reproductive function and health. The ability to recapitulate folliculogenesis, ovulation, and luteinization in vitro has broad basic, translational, and clinical utility. The most advanced in vitro follicle growth systems maintain the follicle's three-dimensional (3D) architecture, which is crucial for the development of meiotically competent metaphase II oocytes in humans. Recently, a scaffold-free method for in vitro follicle growth of mouse multilayer secondary follicles was developed and validated. For this, custom 3D printed molds were used to micropattern agarose with microwells that accommodate the volumetric expansion of follicles. Follicles grown in this scaffold-free environment showed comparable hormone production and viability relative to well-established alginate-based encapsulated in vitro follicle growth (eIVFG) systems. Importantly, agarose microwells are a scalable method, less technically demanding, and show improved follicle growth and ovulation rates relative to eIVFG. This methodology produces customizable molds that are biocompatible with the oocyte, a cell highly sensitive to material-specific leachates and other environmental contaminants. Further, follicles in this system are cultured in the same focal plane, enabling real-time timelapse imaging and analysis. To increase the accessibility of this new approach, this article details the methods needed to design and 3D-print master molds, create silicone molds for 24- or 96-well plates, and culture isolated multilayer secondary ovarian follicles in the agarose molds. This setup can also be integrated with a cost-effective time-lapse imaging system, enabling morphokinetic analysis. In addition, molds can be paraffin-embedded for downstream histological analyses. Overall, this user-friendly method is a versatile tool for follicle culture and can be customized further to promote the differentiation and maturation of germ cells within the context of the follicle to sustain complete in vitro gametogenesis.

  PublisherOA PDFDOI

• Robotic Optical Coherence Tomography With Expanded Three-Dimensional Field-of-View Using Point-Cloud-Based Volumetric Montaging

  IEEE Transactions on Medical Imaging · 2025-06-17 · 3 citations

  articleOpen accessSenior author

  Imaging complex, non-planar anatomies with optical coherence tomography (OCT) is limited by the optical field of view (FOV) in a single volumetric acquisition. Combining linear mechanical translation with OCT extends the FOV but suffers from inflexibility in imaging non-planar anatomies. We report the robotic OCT to fill this gap. To address challenges in volumetric reconstruction associated with the robotic movement accuracy being two orders of magnitudes worse than OCT imaging resolution, we developed a volumetric montaging algorithm. To test the robotic OCT, we imaged the entire circumferential aqueous humor outflow pathway, whose imaging has the potential to customize glaucoma surgeries but is typically constrained by the FOV in mice in vivo. We acquired volumetric OCT data at different robotic poses and reconstructed the entire anterior segment of the eye. From the segmented Schlemm's canal volume, we showed its circumferentially heterogeneous morphology; we also revealed a segmental nature in the circumferential distribution of collector channels with spatial features as small as a few micrometers.

  PublisherOA PDFDOI

• Visualization of nonlinear optics in a microresonator

  ArXiv.org · 2025-07-07

  preprintOpen access1st authorCorresponding

  A precise understanding of nonlinear optical phenomena in whispering gallery mode (WGM) microresonators is crucial for developing next-generation integrated photonic devices. Applications include on-chip sensors for biomedical use, optical memories for all-optical networks and frequency combs for optical clocks. However, our ability to spatially localize nonlinear optical processes within microresonators has been limited because optical feedback is often only collected through a bus waveguide. In this study, we present the direct visualization of nonlinear optical processes using scattering patterns captured by a short-wave infrared (SWIR) camera. Through systematic analysis of these scattering patterns, we can distinguish between different nonlinear effects occurring within the microresonator. Direct imaging of nonlinear processes in microresonators can significantly impact many applications, including the optimization of soliton frequency combs, real-time debugging of photonic circuits, microresonator-based memories, and chip-based data switching in telecom circuits.

  PublisherOA PDFDOI

• Rapid Polarization-Controlled Depth Sensing and Imaging with an Electrically Tunable Metalens

  Nano Letters · 2025-06-02 · 16 citations

  article

  We demonstrate an electrically tunable metalens that combines hydrogenated amorphous silicon (a-Si:H) meta-atoms with a liquid crystal (LC) layer for rapid polarization-controlled depth sensing and imaging. Two independent focusing profiles for left-circularly polarized (LCP) light and right-circularly polarized (RCP) light are encoded via propagation and geometric phases in a single metasurface. Adjusting the LC voltage and the incident polarization among the LCP, RCP, and their superposition enables millisecond-scale reconfiguration. Under pure circular polarization, the metalens yields a single high-fidelity focal spot or an image. Linearly polarized light produces two rotating images, whose relative orientation encodes object depth. Experiments match theory and confirm a full π rotation of the image during focal scanning. The device offers a compact, real-time platform for imaging and depth sensing in microscopy, holography, and adaptive optics.

  PublisherDOI

• Machine-Learning-Based Automated Schlemm’s Canal Volumetric Segmentation for Optical Coherence Tomography

  Chemical & Biomedical Imaging · 2025-11-11

  articleOpen accessSenior authorCorresponding
  PublisherDOI

Recent grants

• Clinical glaucoma management enabled by visible-light OCT

  NIH · $3.2M · 2021–2026

• In Vivo Function and Metabolism Evaluation of Glaucomatous RGCs by Two-Photon Scanning Laser Ophthalmology

  NIH · $2.7M · 2023–2028

• Development of spectroscopic Single-Molecule Localization Microscopy

  NIH · $1.2M · 2020–2025

• Investigating nanoscale neuronal damages in early glaucoma towards clinical optical detection

  NIH · $2.0M · 2018–2024

• Community Engagement

  NIH · $11.5M · 2020–2026

Frequent coauthors

• Cheng Sun

  Evanston Hospital

  76 shared

• Lihong V. Wang

  California Institute of Technology

  57 shared

• Konstantin Maslov

  California Institute of Technology

  53 shared

• Shuliang Jiao

  Florida International University

  43 shared

• Biqin Dong

  Fudan University

  43 shared

• Siyu Chen

  Nanjing University of Science and Technology

  42 shared

• Wenzhong Liu

  Huazhong University of Science and Technology

  38 shared

• Ji Yi

  37 shared

Education

• Ph.D., Biomedical Engineering

  Texas A&M University

  2006