scholarly journals Hydrogels for light delivery in in vivo optogenetic applications

Author(s):  
Sonja Johannsmeier ◽  
Maria L. Torres-Mapa ◽  
Tammo Ripken ◽  
Dag Heinemann ◽  
Alexander Heisterkamp
Keyword(s):  
Author(s):  
Leonardo Sileo ◽  
Marco Pisanello ◽  
Andrea Della Patria ◽  
Mohamed S. Emhara ◽  
Ferruccio Pisanello ◽  
...  
Keyword(s):  

F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 161
Author(s):  
Karin Ried ◽  
Avni Sali ◽  
Michelle Wang ◽  
Brian Meade ◽  
Donald Murphy

Background: An increasing number of patients seek complementary therapies for cancer treatment, the leading cause of death in the developed world. Photodynamic therapy (PDT), the combination of light and a photosensitiser agent, has provided some promising results in cancer therapy. New photosensitiser agents are continuously being developed to improve tolerability and effectiveness. There is a need to objectively evaluate clinical data from PDT patients.Methods: Here we report a case series using the new sublingually administered, chlorophyll-based photosensitiser Photosoft®E4 and an external laser light in a group of ten adult cancer patients not undergoing other concurrent therapies. PDT was administered for three treatment cycles with an average of 14 light treatments per patient, consisting of agent administration and laser treatment on alternate days over 3 months. Safety, tolerability and effectiveness on tumour palliation were monitored. Results: Patients in this study presented with a variety of cancer types and stages; half of the patients had breast cancer, and 40% had metastases. We found Photosoft®E4 to be safe and highly tolerable. However, overall disease status was not improved in our group of patients. Conclusions: Future research is required to determine the bioavailability of Photosoft®E4 and its uptake in tumour tissue, pharmacokinetics and dosing regimen, as well as the best mode of light delivery for the in vivo sensitiser activation.


2018 ◽  
Vol 115 (7) ◽  
pp. 1469-1474 ◽  
Author(s):  
Akshaya Bansal ◽  
Fengyuan Yang ◽  
Tian Xi ◽  
Yong Zhang ◽  
John S. Ho

An emerging class of targeted therapy relies on light as a spatially and temporally precise stimulus. Photodynamic therapy (PDT) is a clinical example in which optical illumination selectively activates light-sensitive drugs, termed photosensitizers, destroying malignant cells without the side effects associated with systemic treatments such as chemotherapy. Effective clinical application of PDT and other light-based therapies, however, is hindered by challenges in light delivery across biological tissue, which is optically opaque. To target deep regions, current clinical PDT uses optical fibers, but their incompatibility with chronic implantation allows only a single dose of light to be delivered per surgery. Here we report a wireless photonic approach to PDT using a miniaturized (30 mg, 15 mm3) implantable device and wireless powering system for light delivery. We demonstrate the therapeutic efficacy of this approach by activating photosensitizers (chlorin e6) through thick (>3 cm) tissues inaccessible by direct illumination, and by delivering multiple controlled doses of light to suppress tumor growth in vivo in animal cancer models. This versatility in light delivery overcomes key clinical limitations in PDT, and may afford further opportunities for light-based therapies.


2019 ◽  
Vol 41 (6) ◽  
pp. 319-335 ◽  
Author(s):  
Laurie J. Rich ◽  
Sarah R. Chamberlain ◽  
Daniela R. Falcone ◽  
Robert Bruce ◽  
Andrew Heinmiller ◽  
...  

Photoacoustic imaging (PAI) is an emerging biomedical imaging technique that utilizes a combination of light and ultrasound to detect photoabsorbers embedded within tissues. While the clinical utility of PAI has been widely explored for several applications, limitations in light penetration and detector sensitivity have restricted these studies to mostly superficial sites. Given the importance of PA signal generation and detection on light delivery and ultrasound detector frequency, there is an ongoing effort to optimize these parameters to enhance photoabsorber detection at increased depths. With this in mind, in this study we examined performance benchmarks of a commercially available PAI/ultrasound linear array system when using different imaging frequencies and light delivery schemes. A modified light fiber jacket providing focused light delivery (FLD) at the center of the probe was compared with the built-in fiber optics lining the length of the probe. Studies were performed in vitro to compare performance characteristics such as imaging resolution, maximum imaging depth, and sensitivity to varying hematocrit concentration for each frequency and light delivery method. Monte Carlo simulations of each light delivery method revealed increased light penetration with FLD. In tissue-mimicking phantoms, vascular channels used to simulate blood vessels could be visualized at a depth of 2.4 cm when lowering imaging frequency and utilizing FLD. Imaging at lower frequencies with FLD also enabled enhanced detection of varying hematocrit concentration levels at increased depths, although lateral imaging resolution was reduced. Finally, a proof of concept in vivo probe comparison study in a mouse tumor model provided supportive evidence of our in vitro results. Collectively, our findings show that adjusting imaging frequency and applying FLD can be a straightforward approach for improving PAI performance.


2019 ◽  
Vol 5 (12) ◽  
pp. eaay1211 ◽  
Author(s):  
Jiamiao Yang ◽  
Lei Li ◽  
Anton A. Shemetov ◽  
Sangjun Lee ◽  
Yuan Zhao ◽  
...  

Focusing light deep by engineering wavefronts toward guide stars inside scattering media has potential biomedical applications in imaging, manipulation, stimulation, and therapy. However, the lack of endogenous guide stars in biological tissue hinders its translations to in vivo applications. Here, we use a reversibly switchable bacterial phytochrome protein as a genetically encoded photochromic guide star (GePGS) in living tissue to tag photons at targeted locations, achieving light focusing inside the tissue by wavefront shaping. As bacterial phytochrome-based GePGS absorbs light differently upon far-red and near-infrared illumination, a large dynamic absorption contrast can be created to tag photons inside tissue. By modulating the GePGS at a distinctive frequency, we suppressed the competition between GePGS and tissue motions and formed tight foci inside mouse tumors in vivo and acute mouse brain tissue, thus improving light delivery efficiency and specificity. Spectral multiplexing of GePGS proteins with different colors is an attractive possibility.


2016 ◽  
Author(s):  
E. Ronzitti ◽  
R. Conti ◽  
E. Papagiakoumou ◽  
D. Tanese ◽  
V. Zampini ◽  
...  

ABSTRACTOptogenetic neuronal network manipulation promises to at last unravel a long-standing mystery in neuroscience: how does microcircuit activity causally relate to behavioral and pathological states? The challenge to evoke spikes with high spatial and temporal complexity necessitates further joint development of light-delivery approaches and custom opsins. Two-photon scanning and parallel illumination strategies applied to ChR2- and C1V1-expressing neurons demonstrated reliable, in-depth generation of action potentials both in-vitro and in-vivo, but thus far lack the temporal precision necessary to induce precisely timed spiking events. Here, we show that efficient current integration enabled by two-photon holographic amplified laser illumination of Chronos, a highly light-sensitive and fast opsin, can evoke spikes with submillisecond precision and repeated firing up to 100 Hz. These results pave the way for optogenetic manipulation with the spatial and temporal sophistication necessary to mimic natural microcircuit activity.


2018 ◽  
Author(s):  
Niall McAlinden ◽  
Yunzhou Cheng ◽  
Robert Scharf ◽  
Enyuan Xie ◽  
Erdan Gu ◽  
...  

AbstractWe present an electrically addressable optrode array capable of delivering light to 181 sites in the brain, each providing sufficient light to optogenetically excite hundreds of neurons in vivo, developed with the aim to allow behavioural studies in large mammals. The device is a glass microneedle array directly integrated with a custom fabricated microLED device, which delivers light to 100 needle tips and 81 interstitial surface sites, giving 2-level optogenetic excitation of neurons in vivo. Light delivery and thermal properties are evaluated, with the device capable of peak irradiances > 80 mW/mm2 per needle at 50 ms pulse widths with tissue temperature increase less than 1 °C. Future designs are explored through optical and thermal modelling and benchmarked against the current device.


Author(s):  
S. Phyllis Steamer ◽  
Rosemarie L. Devine

The importance of radiation damage to the skin and its vasculature was recognized by the early radiologists. In more recent studies, vascular effects were shown to involve the endothelium as well as the surrounding connective tissue. Microvascular changes in the mouse pinna were studied in vivo and recorded photographically over a period of 12-18 months. Radiation treatment at 110 days of age was total body exposure to either 240 rad fission neutrons or 855 rad 60Co gamma rays. After in vivo observations in control and irradiated mice, animals were sacrificed for examination of changes in vascular fine structure. Vessels were selected from regions of specific interest that had been identified on photomicrographs. Prominent ultrastructural changes can be attributed to aging as well as to radiation treatment. Of principal concern were determinations of ultrastructural changes associated with venous dilatations, segmental arterial stenosis and tortuosities of both veins and arteries, effects that had been identified on the basis of light microscopic observations. Tortuosities and irregularly dilated vein segments were related to both aging and radiation changes but arterial stenosis was observed only in irradiated animals.


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