Xose Luis Dean-Ben

University of Zurich | UZH

Efficient drug delivery remains a significant challenge in modern medicine and pharmaceutical research. Micrometer‐scale robots have recently emerged as a promising solution to enhance the precision of drug administration through remotely controlled navigation within microvascular networks. Real‐time tracking is crucial for accurate guidance and co...

INTRODUCTION Transcranial pulse stimulation (TPS) is increasingly being investigated as a promising potential treatment for Alzheimer's disease (AD). Although the safety and preliminary clinical efficacy of TPS short pulses have been supported by neuropsychological scores in treated AD patients, its fundamental mechanisms are uncharted. METHODS He...

Resting-state functional connectivity (rsFC) has been essential to elucidate the intricacy of brain organization, further revealing clinical biomarkers of neurological disorders. Although functional magnetic resonance imaging (fMRI) remains a cornerstone in the field of rsFC recordings, its interpretation is often hindered by the convoluted physiol...

Optoacoustic imaging offers label‐free multi‐parametric characterization of cerebrovascular morphology and hemodynamics at depths and spatiotemporal resolution unattainable with optical microscopy. Effective imaging depth can greatly be enhanced by employing photons in the second near‐infrared (NIR‐II) window. However, diminished absorption by hemo...

Localization optoacoustic tomography (LOT) has recently emerged as a transformative super‐resolution technique breaking through the acoustic diffraction limit in deep‐tissue optoacoustic (OA) imaging via individual localization and tracking of particles in the bloodstream. However, strong light absorption in red blood cells has previously restricte...

Purpose Metabolism and bioenergetics in the central nervous system play important roles in the pathophysiology of Parkinson’s disease (PD). Here, we employed a multimodal imaging approach to assess oxygenation changes in the spinal cord of the transgenic M83 murine model of PD overexpressing the mutated A53T alpha-synuclein form in comparison with...

Optoacoustic (OA) tomography is a powerful noninvasive preclinical imaging tool enabling high resolution whole-body visualization of biodistribution and dynamics of molecular agents. The technique yet lacks endogenous soft-tissue contrast, which often hampers anatomical navigation. Herein, we devise spiral volumetric optoacoustic and ultrasound (SV...

Expanding fluorescence bioimaging into the second near-infrared spectrum (NIR-II, 1000-1700 nm) unlocks advanced possibilities for diagnostics and therapeutics, offering superior tissue penetration and resolution. Two-dimensional copper tetrasilicate (CTS) pigments (MCuSi4O10, M = Ca, Sr, Ba) are known for their brightness and stability, yet synthe...

A Widespread clinical adoption of optoacoustic tomography (OAT) depends on technological advancements in handheld probes that can offer immediate image feedback during the scanning process. Field programmable gate arrays (FPGA) can facilitate the design of lightweight, dynamically configurable handheld probes at an affordable cost and power envelop...

Optoacoustic (OA) imaging offers powerful capabilities for interrogating biological tissues with rich optical absorption contrast while maintaining high spatial resolution for deep tissue observations. The spectrally distinct absorption of visible and near-infrared photons by endogenous tissue chromophores facilitates extraction of diverse anatomic...

Noninvasive monitoring of cardiac development can potentially prevent cardiac anomalies in adulthood. Mouse models provide unique opportunities to study cardiac development and disease in mammals. However, high‐resolution noninvasive functional analyses of murine embryonic cardiac models are challenging because of the small size and fast volumetric...

Optoacoustic (OA) imaging has achieved tremendous progress with state-of-the-art systems providing excellent functional and molecular contrast, centimeter scale penetration into living tissues, and ultrafast imaging performance, making it highly suitable for handheld imaging in the clinics. OA can greatly benefit from efficient integration with ult...

Tendon injuries resulting from accidents and aging are increasing globally. However, key tendon functional parameters such as microvascularity and oxygen perfusion remain inaccessible via the currently available clinical diagnostic tools, resulting in disagreements on optimal treatment options. Here, a new noninvasive method for anatomical and func...

Monitoring brain responses to ultrasonic interventions is becoming an important pillar of a growing number of applications employing acoustic waves to actuate and cure the brain. Optical interrogation of living tissues provides a unique means for retrieving functional and molecular information related to brain activity and disease-specific biomarke...

Given its direct relationship to tissue metabolism and various pathological processes, 3D mapping of blood oxygen saturation (sO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> ) is essential for advancing our knowledge on oxygen delivery to tissues and evaluating therapeutic efficacy. Optoacou...

Major biological discoveries are made by interrogating living organisms with light. However, the limited penetration of un-scattered photons within biological tissues limits the depth range covered by optical methods. Deep-tissue imaging is achieved by combining light and ultrasound. Optoacoustic imaging exploits the optical generation of ultrasoun...

Emerging evidence indicates crosstalk between the brain and hematopoietic system following cerebral ischemia. Here, we investigated metabolism and oxygenation in the spleen and spinal cord in a transient middle cerebral artery occlusion (tMCAO) model. Sham-operated and tMCAO mice underwent [ 18 F]fluorodeoxyglucose (FDG)-positron emission tomograph...

Non-alcoholic fatty liver disease (NAFLD) is an umbrella term referring to a group of conditions associated to fat deposition and damage of liver tissue. Early detection of fat accumulation is essential to avoid progression of NAFLD to serious pathological stages such as liver cirrhosis and hepatocellular carcinoma. Methods: We exploited the unique...

Background Abnormal alpha-synuclein and iron accumulation in the brain play an important role in Parkinson’s disease (PD). Herein, we aim at visualizing alpha-synuclein inclusions and iron deposition in the brains of M83 (A53T) mouse models of PD in vivo . Methods Fluorescently labelled pyrimidoindole-derivative THK-565 was characterized by using...

Multimodal imaging increases the value of stand‐alone modalities by enabling simultaneous multiparametric characterization of biological tissues in vivo. Particularly, optoacoustic (OA) tomography has enabled bringing optical imaging advantages to previously unattainable depths and is currently being hybridized with other imaging technologies for e...

Super-resolution optoacoustic imaging of microvascular structures deep in mammalian tissues has so far been impeded by strong absorption from densely-packed red blood cells. Here we devised 5 µm biocompatible dichloromethane-based microdroplets exhibiting several orders of magnitude higher optical absorption than red blood cells at near-infrared wa...

Optoacoustic tomography (OAT) provides a non-invasive means to characterize cerebral hemodynamics across an entire murine brain while attaining multi-parametric readouts not available with other modalities. This unique capability can massively impact our understanding of brain function. However, OAT largely lacks the soft tissue contrast required f...

Optoacoustic tomography is commonly performed with bulky and expensive short-pulsed solid-state lasers providing high per-pulse energies in the millijoule range. Light emitting diodes (LEDs) represent a cost-effective and portable alternative for optoacoustic signal excitation that can additionally provide excellent pulse-to-pulse stability. Herein...

Fast tracking of biological dynamics across multiple murine organs using the currently commercially available whole-body preclinical imaging systems is hindered by their limited contrast, sensitivity and spatial or temporal resolution. Spiral volumetric optoacoustic tomography (SVOT) provides optical contrast, with an unprecedented level of spatial...

High-intensity focused ultrasound (HIFU) enables localized ablation of biological tissues by capitalizing on the synergistic effects of heating and cavitation. Monitoring of those effects is essential for improving the efficacy and safety of HIFU interventions. Herein, we suggest a hybrid optoacoustic-ultrasound (OPUS) approach for real-time assess...

Major biological discoveries have been made by interrogating living organisms with light. However, the limited penetration of unscattered photons within biological tissues severely limits the depth range covered by optical methods. Deep-tissue imaging has been achieved by combining light and ultrasound. Optoacoustic imaging uniquely exploits optica...

Optoacoustic (OA, photoacoustic) imaging synergistically combines rich optical contrast with the resolution of ultrasound within light‐scattering biological tissues. Contrast agents have become essential to boost deep‐tissue OA sensitivity and fully exploit the capabilities of state‐of‐the‐art OA imaging systems, thus facilitating the clinical tran...

Optoacoustic tomography has been established as a powerful modality for preclinical imaging. However, efficient whole-body imaging coverage has not been achieved owing to the arduous requirement for continuous acoustic coupling around the animal. In this work, we introduce panoramic (3600) head-to-tail 3D imaging of mice with spiral volumetric opto...

Progress in brain research critically depends on the development of next-generation multi-modal imaging tools capable of capturing transient functional events and multiplexed contrasts noninvasively and concurrently, thus enabling a holistic view of dynamic events in vivo. Here we report on a hybrid magnetic resonance and optoacoustic tomography (M...

Imaging modalities capable of visualizing the human brain have led to major advances in neurology and brain research. Multi-spectral optoacoustic tomography (MSOT) has gained importance for studying cerebral function in rodent models due to its unique capability to map changes in multiple hemodynamic parameters and to directly visualize neural acti...

Functional magnetic resonance imaging (fMRI) has massively contributed to the understanding of mammalian brain function. However, the origin and interpretation of the blood oxygen level‐dependent (BOLD) signals retrieved by fMRI remain highly disputed. This article reports on the development of a fully hybridized system enabling concurrent function...

Multi-modal imaging is essential for advancing our understanding of brain function and unraveling pathophysiological processes underlying neurological and psychiatric disorders. Magnetic resonance (MR) and optoacoustic (OA) imaging have been shown to provide highly complementary contrasts and capabilities for preclinical neuroimaging. True integrat...

Detailed characterization of microvascular alterations requires high‐resolution 3D imaging methods capable of providing both morphological and functional information. Existing optical microscopy tools are routinely used for microangiography, yet offer suboptimal trade‐offs between the achievable field of view and spatial resolution with the intense...

Optoacoustic (OA, photoacoustic) imaging capitalizes on the low scattering of ultrasound within biological tissues to provide optical absorption-based contrast with high resolution at depths not reachable with optical microscopy. For deep tissue imaging applications, OA image formation commonly relies on acoustic inversion of time-resolved tomograp...

Fast three-dimensional imaging of freely-swimming zebrafish is essential to understand the link between neuronal activity and behavioral changes during epileptic seizures. Studying the complex spatiotemporal patterns of neuronal activity at the whole-brain or -body level typically requires physical restraint, thus hindering the observation of unper...

Optoacoustic mesoscopy combines rich optical absorption contrast with high spatial resolution at tissue depths beyond reach for microscopic techniques employing focused light excitation. The mesoscopic imaging performance is commonly hindered by the use of inaccurate delay-and-sum reconstruction approaches and idealized modeling assumptions. In pri...

Multispectral optoacoustic tomography (MSOT) is an emerging optical imaging method providing multiplex molecular and functional information from the rodent brain. It can be greatly augmented by magnetic resonance imaging (MRI) which offers excellent soft-tissue contrast and high-resolution brain anatomy. Nevertheless, registration of MSOT-MRI image...

Non-alcoholic fatty liver disease (NAFLD) is an umbrella term referring to a group of conditions associated to fat deposition and damage of liver tissue. Early detection of fat accumulation is essential to avoid progression of NAFLD to serious pathological stages such as liver cirrhosis and hepatocellular carcinoma. We exploited the unique capabili...

Emerging evidence indicates crosstalk between the brain and the hematopoietic system follow-ing cerebral ischemia. Here, we investigated metabolism and oxygenation in the spleen and spinal cord in a transient middle cerebral artery occlusion (tMCAO) mouse model that is wide-ly used in focal cerebral ischemia research. Naive, sham and tMCAO mice und...

Neuroimaging Decoupling the complex interplay of neurovascular coupling and dynamical physiological states has remained challenging when employing single‐modality functional neuroimaging readings. In article number 2105588, Shy Shoham, Daniel Razansky, and co‐workers devise a hybrid fluorescence optoacoustic tomography (FLOT) platform combined with...

Deposits of amyloid-β (Aβ) in the brains of rodents can be analysed by invasive intravital microscopy on a submillimetre scale, or via whole-brain images from modalities lacking the resolution or molecular specificity to accurately characterize Aβ pathologies. Here we show that large-field multifocal illumination fluorescence microscopy and panoram...

Modern optical neuroimaging approaches are expanding the ability to elucidate complex brain function. Diverse imaging contrasts enable direct observation of neural activity with functional sensors along with the induced hemodynamic responses. To date, decoupling the complex interplay of neurovascular coupling and dynamical physiological states has...

Optoacoustic (OA) imaging is based on excitation of biological tissues with nanosecond-duration laser pulses followed by subsequent detection of ultrasound waves generated via light-absorption-mediated thermoelastic expansion. OA imaging features a powerful combination between rich optical contrast and high resolution in deep tissues. This enabled...

Purpose Abnormal tau accumulation within the brain plays an important role in tauopathies such as Alzheimer’s disease and frontotemporal dementia. High-resolution imaging of tau deposits at the whole-brain scale in animal disease models is highly desired. Methods We approached this challenge by non-invasively imaging the brains of P301L mice of 4-...

Imaging modalities capable of visualizing the human brain have led to major advances in neurology and brain research. Multi-spectral optoacoustic tomography (MSOT) has gained importance for studying cerebral function in rodent models due to its unique capability to map changes in multiple hemodynamic parameters and to directly visualize neural acti...

Optoacoustic tomography (OAT) has recently been advanced toward ultrafast volumetric imaging frame rates in the kilohertz range. As a result, excessive data processing and storage capacity requirements are increasingly being imposed on the imaging systems. OAT data commonly exhibit significant sparsity across the spatial, temporal or spectral domai...

Mobile microrobots hold remarkable potential to revolutionize health care by enabling unprecedented active medical interventions and theranostics, such as active cargo delivery and microsurgical manipulations in hard-to-reach body sites. High-resolution imaging and control of cell-sized microrobots in the in vivo vascular system remains an unsolved...

Reflection ultrasound computed tomography (RUCT) attains optimal image quality from objects that can be fully accessed from multiple directions, such as the human breast or small animals. Owing to the full-view tomography approach based on compounding of images taken from multiple angles, RUCT effectively mitigates several deficiencies afflicting c...

Optoacoustic mesoscopy (OAM) retrieves anatomical and functional contrast in vivo at depths not resolvable with optical microscopy. Recent progress on reconstruction algorithms have further advanced its imaging performance to provide high lateral resolution ultimately limited by acoustic diffraction. In this work, a new broadband model‐based OAM (M...