Biomedical Engineering seminars

Visual restoration after decades of blindness is now becoming possible by means of retinal and cortical prostheses, as well as emerging stem cell and gene therapeutic approaches. After restoring visual perception, however, a key question remains. Are there optimal means and methods for retraining the visual cortex to process visual inputs, and for learning or relearning to “see”? Up to this point, it has been largely assumed that if the sensory loss is visual, then the rehabilitation focus should also be primarily visual. However, the other senses play a key role in visual rehabilitation due to the plastic repurposing of visual cortex during blindness by audition and somatosensation, and also to the reintegration of restored vision with the other senses. I will present multisensory neuroimaging results, cortical thickness changes, as well as behavioral outcomes for patients with Retinitis Pigmentosa (RP), which causes blindness by destroying photoreceptors in the retina. These patients have had their vision partially restored by the implantation of a retinal prosthesis, which electrically stimulates still viable retinal ganglion cells in the eye. Our multisensory and structural neuroimaging and behavioral results suggest a new, holistic concept of visual rehabilitation that leverages rather than neglects audition, somatosensation, and other sensory modalities.

La resonancia magnética nuclear está basada en el fenómeno del magnetismo nuclear que más aplicaciones ha encontrado para el estudio de enfermedades humanas. Usualmente la señal de RM es recibida y transmitida a distancias cercanas al objeto del que se quiere obtener una imagen. Otra alternativa es emitir y recibir la misma señal de manera remota haciendo uso de guías de onda. Este enfoque tiene la ventaja que se puede aplicar a altos campos magnéticos, la absorción de energía es menor, además es posible cubrir mayores regiones de interés y comodidad para el paciente. Por otro lado, sufre de baja calidad de imagen en algunos casos. En esta ocasión hablaremos de nuestra experiencia haciendo uso de este enfoque empleando una guía de ondas abierta y metamateriales tanto para sistemas clínicos como preclínicos de IRM.

On Thursday February 15th, we will host Victoria Peterson and Julian Neumann. Victoria will tell us about “Spatial filtering to enhance signal processing in invasive neurophysiology”. Besides his scientific presentation on “Closed-loop deep brain stimulation as a neuroprosthetic of dopaminergic circuits – Current evidence and future opportunities”, Julian will give us a glimpse at the person behind the science. The talks will be followed by a shared discussion. Note: The talks will exceptionally be held at 10 ET / 4PM CET. You can register via talks.stimulatingbrains.org to receive the (free) Zoom link!

Sound waves can be used to modify brain activity safely and transiently with unprecedented precision even deep in the brain - unlike traditional brain stimulation methods. In a series of studies in humans and non-human primates, I will show that Transcranial Ultrasound Stimulation (TUS) can have medium- to long-lasting effects. Multiple read-outs allow us to conclude that TUS can perturb neuronal tissues up to 2h after intervention, including changes in local and distributed brain network configurations, behavioural changes, task-related neuronal changes and chemical changes in the sonicated focal volume. Combined with multiple neuroimaging techniques (resting state functional Magnetic Resonance Imaging [rsfMRI], Spectroscopy [MRS] and task-related fMRI changes), this talk will focus on recent human TUS studies.

On Friday, August 31st we will host Stephanie Cernera & Doris Wang! Stephanie Cernera, PhD, is a postdoctoral research fellow in the Starr lab at University of California San Francisco. She will tell us about “Personalized chronic adaptive deep brain stimulation outperforms conventional stimulation in Parkinson’s Disease”. Doris Wang, MD, PhD, is a neurosurgeon and assistant professor at the University of California San Francisco. Apart from her scientific presentation about “Adaptive Deep Brain Stimulation to Treat Gait Disorders in Parkinson’s Disease”, she will give us a glimpse at the “Person behind the science”. The talks will be followed by a shared discussion. You can register via talks.stimulatingbrains.org to receive the (free) Zoom link!

Myopia is predicted to affect 50% of all people worldwide by 2050, and is a risk factor for significant, potentially blinding ocular pathologies, such as retinal detachment and glaucoma. Thus, there is significant motivation to better understand the process of myopigenesis and to develop effective anti-myopigenic treatments. In nearly all cases of human myopia, scleral remodeling is an obligate step in the axial elongation that characterizes the condition. Here I will describe the development of a biomechanical assay based on transient unconfined compression of scleral samples. By treating the scleral as a poroelastic material, one can determine scleral biomechanical properties from extremely small samples, such as obtained from the mouse eye. These properties provide proxy measures of scleral remodeling, and have allowed us to identify all-trans retinoic acid (atRA) as a myopigenic stimulus in mice. I will also describe nascent collaborative work on modeling the transport of atRA in the eye.

Spatial frequency domain imaging (SFDI) is a diffuse optical measurement technique that can quantify tissue optical absorption and reduced scattering on a pixel by-pixel basis. Measurements of absorption at different wavelengths enable the extraction of molar concentrations of tissue chromophores over a wide field, providing a noncontact and label-free means to assess tissue viability, oxygenation, microarchitecture, and molecular content. In this talk, I will describe openSFDI, an open-source guide for building a low-cost, small-footprint, multi-wavelength SFDI system capable of quantifying absorption and reduced scattering as well as oxyhemoglobin and deoxyhemoglobin concentrations in biological tissue. The openSFDI project has a companion website which provides a complete parts list along with detailed instructions for assembling the openSFDI system. I will also review several technological advances our lab has recently made, including the extension of SFDI to the shortwave infrared wavelength band (900-1300 nm), where water and lipids provide strong contrast. Finally, I will discuss several preclinical and clinical applications for SFDI, including applications related to cancer, dermatology, rheumatology, cardiovascular disease, and others.

The eye is a multi-component biological system, where mechanics, optics, transport phenomena and chemical reactions are strictly interlaced, characterized by the typical bio-variability in sizes and material properties. The eye’s response to external action is patient-specific and it can be predicted only by a customized approach, that accounts for the multiple physics and for the intrinsic microstructure of the tissues, developed with the aid of forefront means of computational biomechanics. Our activity in the last years has been devoted to the development of a comprehensive model of the cornea that aims at being entirely patient-specific. While the geometrical aspects are fully under control, given the sophisticated diagnostic machinery able to provide a fully three-dimensional images of the eye, the major difficulties are related to the characterization of the tissues, which require the setup of in-vivo tests to complement the well documented results of in-vitro tests. The interpretation of in-vivo tests is very complex, since the entire structure of the eye is involved and the characterization of the single tissue is not trivial. The availability of micromechanical models constructed from detailed images of the eye represents an important support for the characterization of the corneal tissues, especially in the case of pathologic conditions. In this presentation I will provide an overview of the research developed in our group in terms of computational models and experimental approaches developed for the human cornea.

This talk will present a low-cost protocol for fabricating an easily constructed femtosecond (fs) fiber laser system suitable for routine multiphoton microscopy (1060–1080 nm, 1 W average power, 70 fs pulse duration, 30–70 MHz repetition rate). Concepts well-known in the laser physics community essential to proper laser operation, but generally obscure to biophysicists and biomedical engineers, will be clarified. The parts list (~$13K US dollars), the equipment list (~$40K+), and the intellectual investment needed to build the laser will be described. A goal of the presentation will be to engage with the audience to discuss trade-offs associated with a custom-built fs fiber laser versus purchasing a commercial system. I will also touch on my research group’s plans to further develop this custom laser system for multiplexed cancer imaging as well as recent developments in the field that promise even higher performance fs fiber lasers for approximately the same cost and ease of construction.

Julie Robinson explores what maintaining human life aboard the International Space Station teaches us about Earth. Space habitation requires engineered substitutes for the air, water, surfaces and living systems that our planet supplies. Long-duration occupation of the station has produced lessons about building and operating these life-support systems. The station is also an observing platform for the Earth system below. Robinson connects the engineering lessons of living in space with Earth observations, climate change, and ways that spaceflight can help communities understand environmental change and strengthen their resilience.

Computational imaging seeks to achieve novel capabilities and overcome conventional limitations by combining optics and algorithms. In this seminar, I will discuss two computational imaging technologies developed in Boston University Computational Imaging Systems lab, including Intensity Diffraction Tomography and Computational Miniature Mesoscope. In our intensity diffraction tomography system, we demonstrate 3D quantitative phase imaging on a simple LED array microscope. We develop both single-scattering and multiple-scattering models to image complex biological samples. In our Computational Miniature Mesoscope, we demonstrate single-shot 3D high-resolution fluorescence imaging across a wide field-of-view in a miniaturized platform. We develop methods to characterize 3D spatially varying aberrations and physical simulator-based deep learning strategies to achieve fast and accurate reconstructions. Broadly, I will discuss how synergies between novel optical instrumentation, physical modeling, and model- and learning-based computational algorithms can push the limits in biomedical microscopy and neural imaging.

Neural computations occurring simultaneously in multiple cerebral cortical regions are critical for mediating behaviors. Progress has been made in understanding how neural activity in specific cortical regions contributes to behavior. However, there is a lack of tools that allow simultaneous monitoring and perturbing neural activity from multiple cortical regions. We have engineered a suite of technologies to enable easy, robust access to much of the dorsal cortex of mice for optical and electrophysiological recordings. First, I will describe microsurgery robots that can programmed to perform delicate microsurgical procedures such as large bilateral craniotomies across the cortex and skull thinning in a semi-automated fashion. Next, I will describe digitally designed, morphologically realistic, transparent polymer skulls that allow long-term (+300 days) optical access. These polymer skulls allow mesoscopic imaging, as well as cellular and subcellular resolution two-photon imaging of neural structures up to 600 µm deep. We next engineered a widefield, miniaturized, head-mounted fluorescence microscope that is compatible with transparent polymer skull preparations. With a field of view of 8 × 10 mm2 and weighing less than 4 g, the ‘mini-mScope’ can image most of the mouse dorsal cortex with resolutions ranging from 39 to 56 µm. We used the mini-mScope to record mesoscale calcium activity across the dorsal cortex during sensory-evoked stimuli, open field behaviors, social interactions and transitions from wakefulness to sleep.

Visual restoration is certainly the greatest challenge for brain-machine interfaces with the high pixel number and high refreshing rate. In the recent year, we brought retinal prostheses and optogenetic therapy up to successful clinical trials. Concerning visual restoration at the cortical level, prostheses have shown efficacy for limited periods of time and limited pixel numbers. We are investigating the potential of sonogenetics to develop a non-contact brain machine interface allowing long-lasting activation of the visual cortex. The presentation will introduce our genetic-based brain machine interfaces for visual restoration at the retinal and cortical levels.

We have been developing Brain-Computer Interface (BCI) using electrocorticography (ECoG) [1] , which is recorded by electrodes implanted on brain surface, and magnetoencephalography (MEG) [2] , which records the cortical activities non-invasively, for the clinical applications. The invasive BCI using ECoG has been applied for severely paralyzed patient to restore the communication and motor function. The non-invasive BCI using MEG has been applied as a neurofeedback tool to modulate some pathological neural activities to treat some neuropsychiatric disorders. Although these techniques have been developed for clinical application, BCI is also an important tool to investigate neural function. For example, motor BCI records some neural activities in a part of the motor cortex to generate some movements of external devices. Although our motor system consists of complex system including motor cortex, basal ganglia, cerebellum, spinal cord and muscles, the BCI affords us to simplify the motor system with exactly known inputs, outputs and the relation of them. We can investigate the motor system by manipulating the parameters in BCI system. Recently, we are developing some BCIs to visualize and manipulate our perception and mental imagery. Although these BCI has been developed for clinical application, the BCI will be useful to understand our neural system to generate the perception and imagery. In this talk, I will introduce our study of phantom limb pain [3] , that is controlled by MEG-BCI, and the development of a communication BCI using ECoG [4] , that enable the subject to visualize the contents of their mental imagery. And I would like to discuss how much we can control our cortical activities that represent our perception and mental imagery. These examples demonstrate that BCI is a promising tool to visualize and manipulate the perception and imagery and to understand our consciousness. References 1. Yanagisawa, T., Hirata, M., Saitoh, Y., Kishima, H., Matsushita, K., Goto, T., Fukuma, R., Yokoi, H., Kamitani, Y., and Yoshimine, T. (2012). Electrocorticographic control of a prosthetic arm in paralyzed patients. AnnNeurol 71, 353-361. 2. Yanagisawa, T., Fukuma, R., Seymour, B., Hosomi, K., Kishima, H., Shimizu, T., Yokoi, H., Hirata, M., Yoshimine, T., Kamitani, Y., et al. (2016). Induced sensorimotor brain plasticity controls pain in phantom limb patients. Nature communications 7, 13209. 3. Yanagisawa, T., Fukuma, R., Seymour, B., Tanaka, M., Hosomi, K., Yamashita, O., Kishima, H., Kamitani, Y., and Saitoh, Y. (2020). BCI training to move a virtual hand reduces phantom limb pain: A randomized crossover trial. Neurology 95, e417-e426. 4. Ryohei Fukuma, Takufumi Yanagisawa, Shinji Nishimoto, Hidenori Sugano, Kentaro Tamura, Shota Yamamoto, Yasushi Iimura, Yuya Fujita, Satoru Oshino, Naoki Tani, Naoko Koide-Majima, Yukiyasu Kamitani, Haruhiko Kishima (2022). Voluntary control of semantic neural representations by imagery with conflicting visual stimulation. arXiv arXiv:2112.01223.

My research uses electrophysiological techniques to evaluate normal retinal function, dysfunction caused by blinding retinal diseases and the restoration of function using a variety of therapeutic strategies. We can use our understanding or normal retinal function and disease-related changes to construct optimal therapeutic strategies and evaluate how they ameliorate the effects of disease. Retinitis pigmentosa (RP) is a family of blinding eye diseases caused by photoreceptor degeneration. The absence of the cells that for this primary signal leads to blindness. My interest in RP involves the evaluation of therapies to restore vision: replacing degenerated photoreceptors either with: (1) new stem or other embryonic cells, manipulated to become photoreceptors or (2) prosthetics devices that replace the photoreceptor signal with an electronic signal to light. Glaucoma is caused by increased intraocular pressure and leads to ganglion cell death, which eliminates the link between the retinal output and central visual processing. We are parsing out of the effects of increased intraocular pressure and aging on ganglion cells. Congenital Stationary Night Blindness (CSNB) is a family of diseases in which signaling is eliminated between rod photoreceptors and their postsynaptic targets, rod bipolar cells. This deafferents the retinal circuit that is responsible for vision under dim lighting. My interest in CSNB involves understanding the basic interplay between excitation and inhibition in the retinal circuit and its normal development. Because of the targeted nature of this disease, we are hopeful that a gene therapy approach can be developed to restore night vision. My work utilizes rodent disease models whose mutations mimic those found in human patients. While molecular manipulation of rodents is a fairly common approach, we have recently developed a mutant NIH miniature swine model of a common form of autosomal dominant RP (Pro23His rhodopsin mutation) in collaboration with the National Swine Resource Research Center at University of Missouri. More genetically modified mini-swine models are in the pipeline to examine other retinal diseases.

Controlling biological processes using light has increased the accuracy and speed with which researchers can manipulate many biological processes. Optical control allows for an unprecedented ability to dissect function and holds the potential for enabling novel genetic therapies. However, optogenetic experiments require adequate light sources with spatial, temporal, or intensity control, often a bottleneck for researchers. Here we detail how to build a low-cost and versatile LED illumination system that is easily customizable for different available optogenetic tools. This system is configurable for manual or computer control with adjustable LED intensity. We provide an illustrated step-by-step guide for building the circuit, making it computer-controlled, and constructing the LEDs. To facilitate the assembly of this device, we also discuss some basic soldering techniques and explain the circuitry used to control the LEDs. Using our open-source user interface, users can automate precise timing and pulsing of light on a personal computer (PC) or an inexpensive tablet. This automation makes the system useful for experiments that use LEDs to control genes, signaling pathways, and other cellular activities that span large time scales. For this protocol, no prior expertise in electronics is required to build all the parts needed or to use the illumination system to perform optogenetic experiments.

Restoring hand function is a top priority for individuals with tetraplegia. This challenge motivates considerable research on brain-computer interfaces (BCIs), which bypass damaged neural pathways to control paralyzed or prosthetic limbs. Here, we demonstrate the BCI control of a prosthetic hand using intracortical recordings from the posterior parietal cortex (PPC). As part of an ongoing clinical trial, two participants with cervical spinal cord injury were each implanted with a 96-channel array in the left PPC. Across four sessions each, we recorded neural activity while they attempted to press individual fingers of the contralateral (right) hand. Single neurons modulated selectively for different finger movements. Offline, we accurately classified finger movements from neural firing rates using linear discriminant analysis (LDA) with cross-validation (accuracy = 90%; chance = 17%). Finally, the participants used the neural classifier online to control all five fingers of a BCI hand. Online control accuracy (86%; chance = 17%) exceeded previous state-of-the-art finger BCIs. Furthermore, offline, we could classify both flexion and extension of the right fingers, as well as flexion of all ten fingers. Our results indicate that neural recordings from PPC can be used to control prosthetic fingers, which may help contribute to a hand restoration strategy for people with tetraplegia.