Off-axis holographic laser speckle contrast imaging of blood vessels in tissues

Laser speckle contrast imaging (LSCI) has become one of the most common tools for functional imaging in tissues. Incomplete theoretical description and sophisticated interpretation of measurement results are completely sidelined by a low-cost and simple hardware, fastness, consistent results, and repeatability. In addition to the relatively low measuring volume with around 700   μ m of the probing depth for the visible spectral range of illumination, there is no depth selectivity in conventional LSCI configuration; furthermore, in a case of high NA objective, the actual penetration depth of light in tissues is greater than depth of field (DOF) of an imaging system. Thus, the information about these out-of-focus regions persists in the recorded frames but cannot be retrieved due to intensity-based registration method. We propose a simple modification of LSCI system based on the off-axis holography to introduce after-registration refocusing ability to overcome both depth-selectivity and DOF problems as well as to get the potential possibility of producing a cross-section view of the specimen

Application of optical coherence tomography for in vivo monitoring of the meningeal lymphatic vessels during opening of blood–brain barrier: mechanisms of brain clearing

The meningeal lymphatic vessels were discovered 2 years ago as the drainage system involved in the mechanisms underlying the clearance of waste products from the brain. The blood–brain barrier (BBB) is a gatekeeper that strongly controls the movement of different molecules from the blood into the brain. We know the scenarios during the opening of the BBB, but there is extremely limited information on how the brain clears the substances that cross the BBB. Here, using the model of sound-induced opening of the BBB, we clearly show how the brain clears dextran after it crosses the BBB via the meningeal lymphatic vessels. We first demonstrate successful application of optical coherence tomography (OCT) for imaging of the lymphatic vessels in the meninges after opening of the BBB, which might be a new useful strategy for noninvasive analysis of lymphatic drainage in daily clinical practice. Also, we give information about the depth and size of the meningeal lymphatic vessels in mice. These new fundamental data with the applied focus on the OCT shed light on the mechanisms of brain clearance and the role of lymphatic drainage in these processes that could serve as an informative platform for a development of therapy and diagnostics of diseases associated with injuries of the BBB such as stroke, brain trauma, glioma, depression, or Alzheimer disease

Cerebral venous circulatory disturbance as an informative prognostic marker for neonatal hemorrhagic stroke

Neonatal hemorrhagic stroke (NHS) is a major problem of future generation’s health due to the high rate of death and cognitive disability of newborns after NHS. The incidence of NHS in neonates cannot be predicted by standard diagnostic methods. Therefore, the identification of prognostic markers of NHS is crucial. There is evidence that stress-related alterations of cerebral blood flow (CBF) may contribute to NHS. Here, we assessed the stroke-associated CBF abnormalities for high prognosis of NHS using a new model of NHS induced by sound stress in the pre- and post-stroke state. With this aim, we used interdisciplinary methods such as a histological assay of brain tissues, laser speckle contrast imaging and Doppler coherent tomography to monitor cerebral circulation. Our results suggest that the venous stasis with such symptoms as progressive relaxation of cerebral veins, decrease the velocity of blood flow in them are prognostic markers for a risk of NHS and are an informative platform for a future study of corrections of cerebral venous circulatory disturbance related to NHS

Optical coherence microangiography of the mouse kidney for diagnosis of circulatory disorders

Optical coherence tomography (OCT) has become widespread in clinical applications in which precise three-dimensional functional imaging of living organs is required. Nevertheless, the kidney is inaccessible for the high resolution OCT imaging due to a high light attenuation coefficient of skin and soft tissues that significantly limits the penetration depth of the probing laser beam. Here, we introduce a surgical protocol and fixation scheme that enables functional visualization of kidney’s peritubular capillaries via OCT microangiography. The model of reversible/irreversible glomerulus embolization using drug microcarriers confirms the ability of OCT to detect circulatory disorders. This approach can be used for choosing optimal carriers, their dosages and diagnosis of other blood flow pathologies

Photobiomodulation of lymphatic drainage and clearance: perspective strategy for augmentation of meningeal lymphatic functions

There is a hypothesis that augmentation of the drainage and clearing function of the meningeal lymphatic vessels (MLVs) might be a promising therapeutic target for preventing neurological diseases. Here we investigate mechanisms of photobiomodulation (PBM, 1267 nm) of lymphatic drainage and clearance. Our results obtained at optical coherence tomography (OCT) give strong evidence that low PBM doses (5 and 10 J/cm2) stimulate drainage function of the lymphatic vessels via vasodilation (OCT data on the mesenteric lymphatics) and stimulation of lymphatic clearance (OCT data on clearance of gold nanorods from the brain) that was supported by confocal imaging of clearance of FITC-dextran from the cortex via MLVs. We assume that PBM-mediated relaxation of the lymphatic vessels can be possible mechanisms underlying increasing the permeability of the lymphatic endothelium that allows molecules transported by the lymphatic vessels and explain PBM stimulation of lymphatic drainage and clearance. These findings open new strategies for the stimulation of MLVs functions and non-pharmacological therapy of brain diseases

Pilot study of transcranial photobiomodulation of lymphatic clearance of beta-amyloid from the mouse brain: breakthrough strategies for non-pharmacologic therapy of Alzheimer's disease

In this pilot study, we analyzed effects of transcranial photobiomodulation (tPBM, 1267 nm, 32 J/cm2) on clearance of beta-amyloid (Aβ) from the mouse brain. The immunohistochemical and confocal data clearly demonstrate the significant reduction of deposition of Aβ plaques in mice after tPBM vs. untreated animals. The behavior tests showed that tPBM improved the cognitive, memory and neurological status of mice with Alzheimer’s disease (AD). Using of our original method based on optical coherence tomography (OCT) analysis of clearance of gold nanorods (GNRs) from the brain, we proposed possible mechanism underlying tPBM-stimulating effects on clearance of Aβ via the lymphatic system of the brain and the neck. These results open breakthrough strategies for a non-pharmacological therapy of Alzheimer’s disease and clearly demonstrate that tPBM might be a promising therapeutic target for preventing or delaying Alzheimer’s disease

Stress plays provoking role in hypertension-related stroke: Injuries of blood-brain barrier function

Chronic hypertension itself does not cause stroke but significantly decreases the resistant to stroke induced by stress due to exhausting of adaptive capacity of cerebral endothelium and decrease resistance of blood-brain barrier to stress

The stress and vascular catastrophes in newborn rats: mechanisms preceding and accompanying the brain hemorrhages

In this study, we analyzed the time-depended scenario of stress response cascade preceding and accompanying brain hemorrhages in newborn rats using an interdisciplinary approach based on: a morphological analysis of brain tissues, coherent-domain optical technologies for visualization of the cerebral blood flow, monitoring of the cerebral oxygenation and the deformability of red blood cells (RBCs). Using a model of stress-induced brain hemorrhages (sound stress, 120 dB, 370 Hz), we studied changes in neonatal brain 2, 4, 6, 8 h after stress (the pre-hemorrhage, latent period) and 24 h after stress (the post-hemorrhage period). We found that latent period of brain hemorrhages is accompanied by gradual pathological changes in systemic, metabolic, and cellular levels of stress. The incidence of brain hemorrhages is characterized by a progression of these changes and the irreversible cell death in the brain areas involved in higher mental functions. These processes are realized via a time-depended reduction of cerebral venous blood flow and oxygenation that was accompanied by an increase in RBCs deformability. The significant depletion of the molecular layer of the prefrontal cortex and the pyramidal neurons, which are crucial for associative learning and attention, is developed as a consequence of homeostasis imbalance. Thus, stress-induced processes preceding and accompanying brain hemorrhages in neonatal period contribute to serious injuries of the brain blood circulation, cerebral metabolic activity and structural elements of cognitive function. These results are an informative platform for further studies of mechanisms underlying stress-induced brain hemorrhages during the first days of life that will improve the future generation's health

Lightsheet-based flow cytometer for whole blood with the ability for the magnetic retrieval of objects from the blood flow

Detection and extraction of circulating tumor cells and other rare objects in the bloodstream are of great interest for modern diagnostics, but devices that can solve this problem for the whole blood volume of laboratory animals are still rare. Here we have developed SPIM-based lightsheet flow cytometer for the detection of fluorescently-labeled objects in whole blood. The bypass channel between two blood vessels connected with the external flow cell was used to visualize, detect, and magnetically separate fluorescently-labeled objects without hydrodynamic focusing. Carriers for targeted drug delivery were used as model objects to test the device performance. They were injected into the bloodstream of the rat, detected fluorescently, and then captured from the bloodstream by a magnetic separator prior to filtration in organs. Carriers extracted from the whole blood were studied by a number of in vitro methods

Roadmap on holography

From its inception holography has proven an extremely productive and attractive area of research. While specific technical applications give rise to 'hot topics', and three-dimensional (3D) visualisation comes in and out of fashion, the core principals involved continue to lead to exciting innovations in a wide range of areas. We humbly submit that it is impossible, in any journal document of this type, to fully reflect current and potential activity; however, our valiant contributors have produced a series of documents that go no small way to neatly capture progress across a wide range of core activities. As editors we have attempted to spread our net wide in order to illustrate the breadth of international activity. In relation to this we believe we have been at least partially successful.This work was supported by Ministerio de Economía, Industria y Competitividad (Spain) under projects FIS2017-82919-R (MINECO/AEI/FEDER, UE) and FIS2015-66570-P (MINECO/FEDER), and by Generalitat Valenciana (Spain) under project PROMETEO II/2015/015