Massachusetts Institute of Technology

Bond-Selective Full-Field Optical Coherence Tomography

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Optical coherence tomography (OCT) is a label-free, non-invasive 3D imaging tool widely used in both biological research and clinical diagnosis. Current OCT modalities can only visualize specimen tomography without chemical information. Here, we report a bondselective full-field OCT (BS-FF-OCT), in which a pulsed mid-infrared laser is used to modulate the OCT signal through the photothermal effect, achieving label-free bond-selective 3D sectioned imaging of highly scattering samples. We first demonstrate BS-FF-OCT imaging of 1 μm PMMA beads embedded in agarose gel. Next, we then show 3D hyperspectral imaging of polypropylene fiber mattress from a standard surgical mask. We then demonstrate BS-FFOCT imaging on biological samples, including cancer cell spheroids and C. elegans. Using an alternative pulse timing configuration, we finally demonstrate the capability of BS-FF-OCT on a bulky and highly scattering 150 μm thick mouse brain slice.

Ultrahigh resolution optical coherence tomography markers of normal aging and early age-related macular degeneration

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Purpose Ultrahigh resolution spectral domain optical coherence tomography (UHR SD-OCT) enables in vivo visualization of micrometric structural markers which differentially associate with normal aging versus age-related macular degeneration (AMD). This study explores the hypothesis that UHR SD-OCT can detect and quantify sub-retinal pigment epithelium (RPE) deposits in early AMD, separating AMD pathology from normal aging. Design Prospective cross-sectional study. Participants 53 non-exudative (dry) AMD eyes from 39 patients, and 63 normal eyes from 39 subjects. Methods Clinical UHR SD-OCT scans were performed using a high-density protocol. Exemplary high-resolution histology and transmission electron microscopy (TEM) images were obtained from archive donor eyes. Three trained readers evaluated and labeled outer retina morphological features, including the appearance of a hypo-reflective split within the RPE – RPE basal lamina (RPE-BL) – Bruch’s membrane (BrM) complex on UHR B...

AI-based clinical assessment of optic nerve head robustness superseding biomechanical testing

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AI-based clinical assessment of optic nerve head robustness superseding biomechanical testing Background/aims To use artificial intelligence (AI) to: (1) exploit biomechanical knowledge of the optic nerve head (ONH) from a relatively large population; (2) assess ONH robustness (ie, sensitivity of the ONH to changes in intraocular pressure (IOP)) from a single optical coherence tomography (OCT) volume scan of the ONH without the need for biomechanical testing and (3) identify what critical three-dimensional (3D) structural features dictate ONH robustness. Methods 316 subjects had their ONHs imaged with OCT before and after acute IOP elevation through ophthalmo-dynamometry. IOP-induced lamina cribrosa (LC) deformations were then mapped in 3D and used to classify ONHs. Those with an average effective LC strain superior to 4% were considered fragile, while those with a strain inferior to 4% robust. Learning from these data, we compared three AI algorithms to predict ONH robustness strictly from a baseline (undeformed) OCT volume: (1) a random forest classifier; (2) an aut...

Endoscopic imaging of white matter fiber tracts using polarization-sensitive optical coherence tomography

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Polarization sensitive optical coherence tomography (PSOCT) has been shown to image and delineate white matter fibers in a label-free manner by revealing optical birefringence within the myelin sheath using a microscope setup. In this proof-of-concept study, we adapt recent advancements in endoscopic PSOCT to perform depth-resolved imaging of white matter structures deep inside intact porcine brain tissue ex-vivo, through a small, rotational fiber probe. The probe geometry is comparable to microelectrodes currently used in neurosurgical interventions. The presented imaging system is mobile, robust, and uses biologically safe levels of optical radiation making it well suited for clinical translation. In neurosurgery, where accuracy is imperative, endoscopic PSOCT through a narrow-gauge fiber probe could provide intra-operative feedback on the location of critical white matter structures. ( Read Full Article )

DFG grants funding to quantify ocular blood flow

The German research foundation provides support to the Pattern Recognition Lab’s ophthalmic imaging group, led by Stefan Ploner, in the amount of more than a quarter million Euro, over a 30-month funding period. With this meanwhile third grant, DFG continues to strengthen a long standing collaboration in OCT(A) motion correction and signal reconstruction between the pattern recognition lab at FAU, led by Prof. Andreas Maier; the Biomedical Optical Imaging and Biophotonics group at MIT, led by the inventor of OCT, Prof. James Fujimoto; and clinicians at the New England Eye Center, led by retinal specialist Prof. Nadia Waheed. In this new project, we will merge two of our major research directions, bringing together retinal blood flow quantification ( Ploner et al., Retina, 2016 ) and OCT motion correction ( Kraus et al., BOEx, 2014 ; Ploner et al., MICCAI, 2022 ). Compared to classic static 3D OCTA vasculature analysis, we will develop methods for eye motion-corrected 4D (time-...

Minimally Invasive Polarization Sensitive Optical Coherence Tomography (PS-OCT) for assessing Pre-OA, a pilot study on technical feasibility

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Efforts to develop chondroprotective approaches to halt osteoarthritis (OA) progression have recently increased. Current imaging techniques are critical in managing advanced OA, but greater resolution is needed to identify reversible stages (pre-OA). Optical coherence tomography (OCT) is a micron scale imaging technology widely used in ophthalmology, cardiology, and neurology. We previously demonstrated that polarization sensitive OCT (PS-OCT) can identify pre-OA in vitro, in animals, and in open surgical fields. This feasibility study examines performing intraarticular PS-OCT using a flexible endocatheter introduced through a stiff 18-gauge spinal needle. Results are critical for designing larger clinical trials examining minimally invasive PS-OCT's ability to identify pre-OA. Design Fifteen patients undergoing arthroscopic partial medial meniscectomy were selected to confirm their risk for rapid progression to OA. Magnetic resonance imaging (MRI) was obtained at time 0 and at 2.5 ...

MEMS-VCSEL swept-source optical coherence tomography for multi-MHz endoscopic …

Swept-source optical coherence tomography (SS-OCT) enables volumetric imaging of subsurface structure, but applications requiring wide fields of view, rapid imaging, and higher resolutions have been challenging because of the need for multi-MHz A-scan rates. Until now, achieving multi-MHz A-scan rates has been limited to Fourier-domain mode-locked lasers or stretched-pulse lasers. We describe a microelectromechanical-system, vertical-cavity surface-emitting laser (MEMS-VCSEL) for SS-OCT at A-scan rates of 2.4 and 3.0 MHz using a dual-channel acquisition system. Dual-channel operation enables simultaneous acquisition of Mach-Zehnder interferometer (MZI) fringes for sweep-to-sweep calibration and resampling, overcoming inherent optical clock limitations in state-of-the-art digitizers. We demonstrate structural OCT and OCT angiography (OCTA) imaging of the swine gastrointestinal tract using a suite of endoscopic devices, including a 3.2 mm diameter micromotor catheter, a 12 mm diameter...

Measuring collagen injury depth for burn severity determination using polarization sensitive optical coherence tomography

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Determining the optimal treatment course for a dermatologic burn wound requires knowledge of the wound's severity, as quantified by the depth of thermal damage. In current clinical practice, burn depth is inferred based exclusively on superficial visual assessment, a method which is subject to substantial error rates in the classification of partial thickness (second degree) burns. Here, we present methods for direct, quantitative determination of the depth extent of injury to the dermal collagen matrix using polarization-sensitive optical coherence tomography (PS-OCT). By visualizing the depth-dependence of the degree of polarization of light in the tissue, rather than cumulative retardation, we enable direct and volumetric assessment of local collagen status. We further augment our PS-OCT measurements by visualizing adnexal structures such as hair follicles to relay overall dermal viability in the wounded region. Our methods, which we have validated ex vivo with matched histology,...

Light-sheet photonic force optical coherence elastography for high-throughput quantitative 3D micromechanical imaging

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Quantitative characterisation of micro-scale mechanical properties of the extracellular matrix (ECM) and dynamic cell-ECM interactions can significantly enhance fundamental discoveries and their translational potential in the rapidly growing field of mechanobiology. However, quantitative 3D imaging of ECM mechanics with cellular-scale resolution and dynamic monitoring of cell-mediated changes to pericellular viscoelasticity remain a challenge for existing mechanical characterisation methods. Here, we present light-sheet photonic force optical coherence elastography (LS-pfOCE) to address this need by leveraging a light-sheet for parallelised, non-invasive, and localised mechanical loading. We demonstrate the capabilities of LS-pfOCE by imaging the micromechanical heterogeneity of fibrous collagen matrices and perform live-cell imaging of cell-mediated ECM micromechanical dynamics. By providing access to 4D spatiotemporal variations in the micromechanical properties of 3D biopolymer c...

Optica Names Joseph A. Izatt the 2022 Stephen D. Fantone Distinguished Service Award Recipient

Optica (formerly OSA) is pleased to announce that Joseph A. Izatt, Duke University, USA, has been selected as the 2022 recipient of the Stephen D. Fantone Distinguished Service Award . Izatt is being honored for over 25 years of outstanding service to the optics community and Optica in areas as diverse as publications, conferences, strategic planning, and the Optica Board of Directors. Joseph A. Izatt received his PhD from the Massachusetts Institute of Technology, USA. He is currently the Michael J. Fitzpatrick Professor of Engineering in the Edmund T. Pratt, Jr. School of Engineering. He co-founded Bioptigen and previously held positions at University Hospitals of Cleveland, USA, and Case Western Reserve University, USA. Izatt is a long-time volunteer and leader who has helped shape and strengthen Optica’s conferences, publications, and overall strategy. He has served on many committees and councils, including the Board of Editors, Publications Council, Board of Directors, a...

A novel algorithm for multiplicative speckle noise reduction in ex vivo human brain OCT images

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Optical coherence tomography (OCT) images of ex vivo human brain tissue are corrupted by multiplicative speckle noise that degrades the contrast to noise ratio (CNR) of microstructural compartments. This work proposes a novel algorithm to reduce noise corruption in OCT images that minimizes the penalized negative log likelihood of gamma distributed speckle noise. The proposed method is formulated as a majorize-minimize problem that reduces to solving an iterative regularized least squares optimization. We demonstrate the usefulness of the proposed method by removing speckle in simulated data, phantom data and real OCT images of human brain tissue. We compare the proposed method with state of the art filtering and non-local means based denoising methods. We demonstrate that our approach removes speckle accurately, improves CNR between different tissue types and better preserves small features and edges in human brain tissue. ( Read Full Article )

Ultrahigh resolution spectral-domain optical coherence tomography using the 1000-1600 nm spectral band

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Ultrahigh resolution optical coherence tomography (UHR-OCT) can image microscopic features that are not visible with the standard OCT resolution of 5-15 µm. In previous studies, high-speed UHR-OCT has been accomplished within the visible (VIS) and near-infrared (NIR-I) spectral ranges, specifically within 550-950 nm. Here, we present a spectral domain UHR-OCT system operating in a short-wavelength infrared (SWIR) range from 1000 to 1600 nm using a supercontinuum light source and an InGaAs-based spectrometer. We obtained an axial resolution of 2.6 µm in air, the highest ever recorded in the SWIR window to our knowledge, with deeper penetration into tissues than VIS or NIR-I light. We demonstrate imaging of conduction fibers of the left bundle branch in freshly excised porcine hearts. These results suggest a potential for deep-penetration, ultrahigh resolution OCT in intraoperative applications. ( Read Full Article )

Optical coherence tomography in coronary atherosclerosis assessment and intervention

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Since optical coherence tomography (OCT) was first performed in humans two decades ago, this imaging modality has been widely adopted in research on coronary atherosclerosis and adopted clinically for the optimization of percutaneous coronary intervention. In the past 10 years, substantial advances have been made in the understanding of in vivo vascular biology using OCT. Identification by OCT of culprit plaque pathology could potentially lead to a major shift in the management of patients with acute coronary syndromes. Detection by OCT of healed coronary plaque has been important in our understanding of the mechanisms involved in plaque destabilization and healing with the rapid progression of atherosclerosis. Accurate detection by OCT of sequelae from percutaneous coronary interventions that might be missed by angiography could improve clinical outcomes. In addition, OCT has become an essential diagnostic modality for myocardial infarction with non-obstructive coronary arteries. I...

James Fujimoto named 2022 recipient of the IEEE Medal for Innovations in Healthcare Technology

James Fujimoto, the Elihu Thomson Professor in Electrical Engineering, has been named the 2022 recipient of the IEEE Medal for Innovations in Healthcare Technology. In the award citation, the IEEE lauded Fujimoto “for pioneering the development and commercialization of optical coherence tomography for medical imaging and diagnostics.” Professor Fujimoto is a principal investigator in the Research Laboratory of Electronics (RLE). He received his S.B., S.M., and Ph.D. in EECS from MIT in 1979, 1981, and 1984 respectively. He joined the MIT faculty in 1985 and is currently Elihu Thomson Professor of Electrical Engineering at MIT, Adjunct Professor of Ophthalmology at Tufts University School of Medicine, and Adjunct Professor, Medical University of Vienna (2016-present). Fujimoto’s research involves biomedical imaging, optical coherence tomography (OCT), advanced laser technologies and applications in diverse areas including ophthalmology, endoscopy, cancer detection, ...

Relationship between axial resolution and signal-to-noise ratio in optical coherence tomography

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In optical coherence tomography (OCT), axial resolution and signal-to-noise ratio (SNR) are typically viewed as uncoupled parameters. We show that this is true only for mirror-like surfaces and that in diffuse scattering samples such as biological tissues there is an inherent coupling between axial resolution and measurement SNR. We explain the origin of this coupling and demonstrate that it can be used to achieve increased imaging penetration depth at the expense of resolution. Finally, we argue that this coupling should be considered during OCT system design processes that seek to balance the competing needs of resolution, sensitivity, and system/source complexity. ( Read Full Article )

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