Publications by authors named "Uwe Klemm"

Optoacoustic imaging (OAI) is a unique in vivo imaging technique combining deep tissue penetration with high resolution and molecular sensitivity. OAI relying on strong intrinsic contrast, such as blood hemoglobin, already shows its value in medical diagnostics. However, OAI sensitivity to current extrinsic contrast agents is insufficient and limits its role in detecting disease-related biomarkers.

View Article and Find Full Text PDF

Cyanine derivatives are organic dyes widely used for optical imaging. However, their potential in longitudinal optoacoustic imaging and photothermal therapy remains limited due to challenges such as poor chemical stability, poor photostability, and low photothermal conversion. In this study, we present a new structural modification for cyanine dyes by introducing a strongly electron-withdrawing group (barbiturate), resulting in a new series of barbiturate-cyanine dyes (BC810, BC885, and BC1010) with suppressed fluorescence and enhanced stability.

View Article and Find Full Text PDF

Optoacoustic (or photoacoustic) imaging promises micron-resolution noninvasive bioimaging with much deeper penetration (>cm) than fluorescence. However, optoacoustic imaging of enzyme activity would require loud, photostable, NIR-absorbing molecular contrast agents, which remain unknown. Most organic molecular contrast agents are repurposed fluorophores, with severe shortcomings of photoinstability or phototoxicity under optoacoustic imaging, as consequences of their slow S→S electronic relaxation.

View Article and Find Full Text PDF

Fluorescence molecular endoscopy (FME) is emerging as a "red-flag" technique with potential to deliver earlier, faster, and more personalized detection of disease in the gastrointestinal tract, including cancer, and to gain insights into novel drug distribution, dose finding, and response prediction. However, to date, the performance of FME systems is assessed mainly by endoscopists during a procedure, leading to arbitrary, potentially biased, and heavily subjective assessment. This approach significantly affects the repeatability of the procedures and the interpretation or comparison of the acquired data, representing a major bottleneck towards the clinical translation of the technology.

View Article and Find Full Text PDF
Article Synopsis
  • Hematopoietic stem cells (HSCs) in bone marrow regenerate various blood cell lineages but can be affected by stress, with microRNAs (miRNAs) like miR-221/222 playing a significant role in this process.
  • Research showed that the loss of miR-221/222 in mice led to a drastic reduction in HSC pools and changes in myeloid/erythroid precursor levels, resembling the effects of social stress.
  • Single-cell RNA sequencing identified over 80 genes affected by stress, with specific immediate early genes (IEGs) emerging as potential targets for miR-221/222, linking them to processes that influence blood cell development.
View Article and Find Full Text PDF

In previous studies, Mott cells, an unusual form of plasma cells containing Ig-inclusion bodies, were frequently observed in peripheral lymphoid tissues in our IgM Fc receptor (FcμR)-deficient (KO) mouse strain. Because of discrepancies in the reported phenotypes of different Fcmr KO mouse strains, we here examined two additional available mutant strains and confirmed that such enhanced Mott-cell formation was a general phenomenon associated with FcμR deficiency. Splenic B cells from Fcmr KO mice clearly generated more Mott cells than those from WT mice when stimulated in vitro with LPS alone or a B-1, but not B-2, activation cocktail.

View Article and Find Full Text PDF

The proper design of near-infrared light-absorbing agents enables efficient optoacoustic imaging-guided phototherapy. In particular, several croconaine-based organic agents with excellent optical properties have been recently reported for this purpose. However, most of them absorb light below 800 nm, limiting deep-tissue imaging applications.

View Article and Find Full Text PDF

Test-samples are necessary for the development of emerging imaging approaches such as optoacoustics (OA); these can be used to benchmark new labeling agents and instrumentation, or to characterize image analysis algorithms or the inversion required to form the three-dimensional reconstructions. Alginate beads (AlBes) loaded with labeled mammalian or bacterial cells provide a method of creating defined structures of controllable size and photophysical characteristics and are well-suited for both and use. Here we describe a simple and rapid method for efficient and reproducible production of AlBes with specific characteristics and show three example applications with multispectral OA tomography imaging.

View Article and Find Full Text PDF

Reversibly photo-switchable proteins are essential for many super-resolution fluorescence microscopic and optoacoustic imaging methods. However, they have yet to be used as sensors that measure the distribution of specific analytes at the nanoscale or in the tissues of live animals. Here we constructed the prototype of a photo-switchable Ca sensor based on GCaMP5G that can be switched with 405/488-nm light and describe its molecular mechanisms at the structural level, including the importance of the interaction of the core barrel structure of the fluorescent protein with the Ca receptor moiety.

View Article and Find Full Text PDF
Article Synopsis
  • Scientists are studying lipids because they're linked to obesity and liver diseases, which are becoming more common worldwide.
  • They used a special imaging technique called MSOT to see and measure lipids in the livers of mice with fatty liver disease without needing any dyes.
  • The research shows that MSOT is a helpful tool for understanding liver health and can help check how serious the liver disease is.
View Article and Find Full Text PDF
Article Synopsis
  • Scientists are using a special imaging technique called eMSOT to study how breast tumors react to a chemotherapy drug called Taxotere over 41 days.
  • They found that this drug makes the tumors have lower oxygen levels and shows changes in how blood flows in and around the tumors.
  • This research is important because it could help doctors understand how tumors resist treatment and make better decisions about patient care without needing to do invasive procedures.
View Article and Find Full Text PDF

Contrast enhancement in optoacoustic (photoacoustic) imaging can be achieved with agents that exhibit high absorption cross-sections, high photostability, low quantum yield, low toxicity, and preferential bio-distribution and clearance profiles. Based on advantageous photophysical properties of croconaine dyes, we explored croconaine-based nanoparticles (CR780RGD-NPs) as highly efficient contrast agents for targeted optoacoustic imaging of challenging preclinical tumor targets. Initial characterization of the CR780 dye was followed by modifications using polyethylene glycol and the cancer-targeting c(RGDyC) peptide, resulting in self-assembled ultrasmall particles with long circulation time and active tumor targeting.

View Article and Find Full Text PDF
Article Synopsis
  • The squamous and columnar epithelia are areas in the cervix that can develop cancer, often starting with a process called metaplasia, where one type of cell is replaced by another.
  • Researchers used advanced technology to study the different types of cells in these areas, discovering that they come from different types of stem cells that are controlled by opposite signals from surrounding tissue.
  • In experiments with mice, they found that changes in the tissue can lead to increased growth of certain stem cells, showing how the balance of cells at the transition zone is influenced by different signals in the tissue around them.
View Article and Find Full Text PDF

Optical interrogation of tissues is broadly considered in biomedical applications. Nevertheless, light scattering by tissue limits the resolution and accuracy achieved when investigating sub-surface tissue features. Light carrying optical angular momentum or complex polarization profiles, offers different propagation characteristics through scattering media compared to light with unstructured beam profiles.

View Article and Find Full Text PDF

Understanding temporal and spatial hemodynamic heterogeneity as a function of tumor growth or therapy affects the development of novel therapeutic strategies. In this study, we employed eigenspectra multispectral optoacoustic tomography (eMSOT) as a next-generation optoacoustic method to impart high accuracy in resolving tumor hemodynamics during bevacizumab therapy in two types of breast cancer xenografts (KPL-4 and MDA-MB-468). Patterns of tumor total hemoglobin concentration (THb) and oxygen saturation (sO) were imaged in control and bevacizumab-treated tumors over the course of 58 days (KPL-4) and 16 days (MDA-MB-468), and the evolution of functional vasculature "normalization" was resolved macroscopically.

View Article and Find Full Text PDF

We introduce two photochromic proteins for cell-specific in vivo optoacoustic (OA) imaging with signal unmixing in the temporal domain. We show highly sensitive, multiplexed visualization of T lymphocytes, bacteria, and tumors in the mouse body and brain. We developed machine learning-based software for commercial imaging systems for temporal unmixed OA imaging, enabling its routine use in life sciences.

View Article and Find Full Text PDF

Fluorescence imaging opens new possibilities for intraoperative guidance and early cancer detection, in particular when using agents that target specific disease features. Nevertheless, photon scattering in tissue degrades image quality and leads to ambiguity in fluorescence image interpretation and challenges clinical translation. We introduce the concept of capturing the spatially-dependent impulse response of an image and investigate Spatially Adaptive Impulse Response Correction (SAIRC), a method that is proposed for improving the accuracy and sensitivity achieved.

View Article and Find Full Text PDF

Macrophages are one of the most functionally-diverse cell types with roles in innate immunity, homeostasis and disease making them attractive targets for diagnostics and therapy. Photo- or optoacoustics could provide non-invasive, deep tissue imaging with high resolution and allow to visualize the spatiotemporal distribution of macrophages in vivo. However, present macrophage labels focus on synthetic nanomaterials, frequently limiting their ability to combine both host cell viability and functionality with strong signal generation.

View Article and Find Full Text PDF

Objective: Fluorescence molecular imaging (FMI) has emerged as a promising tool for surgical guidance in oncology, with one of the few remaining challenges being the ability to offer quality control and data referencing. This paper investigates the use of a novel composite phantom to correct and benchmark FMI systems.

Methods: This paper extends on previous work by describing a phantom design that can provide a more complete assessment of FMI systems through quantification of dynamic range and determination of spatial illumination patterns for both reflectance and fluorescence imaging.

View Article and Find Full Text PDF

Τhe morphology, physiology and immunology, of solid tumors exhibit spatial heterogeneity which complicates our understanding of cancer progression and therapy response. Understanding spatial heterogeneity necessitates high resolution in vivo imaging of anatomical and pathophysiological tumor information. We introduce Rhodobacter as bacterial reporter for multispectral optoacoustic (photoacoustic) tomography (MSOT).

View Article and Find Full Text PDF

Advances in genetic engineering have enabled the use of bacterial outer membrane vesicles (OMVs) to deliver vaccines, drugs and immunotherapy agents, as a strategy to circumvent biocompatibility and large-scale production issues associated with synthetic nanomaterials. We investigate bioengineered OMVs for contrast enhancement in optoacoustic (photoacoustic) imaging. We produce OMVs encapsulating biopolymer-melanin (OMV) using a bacterial strain expressing a tyrosinase transgene.

View Article and Find Full Text PDF
Article Synopsis
  • Fluorescence molecular imaging (FMI) is a new way to find and understand cancer during surgery and check-ups, and it has gotten better at spotting glowing agents in real-time.
  • Different FMI systems don’t always give the same results, which can cause problems when doctors use them in hospitals.
  • This study looks at using a special tool called a composite fluorescence phantom to help make sure that different imaging systems work similarly and reliably, so they can be used more effectively in medicine.
View Article and Find Full Text PDF

Fluorescence imaging has been considered for over a half-century as a modality that could assist surgical guidance and visualization. The administration of fluorescent molecules with sensitivity to disease biomarkers and their imaging using a fluorescence camera can outline pathophysiological parameters of tissue invisible to the human eye during operation. The advent of fluorescent agents that target specific cellular responses and molecular pathways of disease has facilitated the intraoperative identification of cancer with improved sensitivity and specificity over nonspecific fluorescent dyes that only outline the vascular system and enhanced permeability effects.

View Article and Find Full Text PDF

Norovirus infection is the main cause of epidemic non-bacterial gastroenteritis in humans. Although human norovirus (HuNoV) infection is self-limiting, it can persist for extended periods of time in immune deficient patients. Due to the lack of robust cell culture and small animal systems, little is known about HuNoV pathogenicity.

View Article and Find Full Text PDF

Regulatory T (Treg) cells expressing Foxp3 transcripton factor are essential for immune homeostasis. They arise in the thymus as a separate lineage from conventional CD4(+)Foxp3(-) T (Tconv) cells. Here, we show that the thymic development of Treg cells depends on the expression of their endogenous cognate self-antigen.

View Article and Find Full Text PDF

A PHP Error was encountered

Severity: Warning

Message: fopen(/var/lib/php/sessions/ci_session22278rsen09qkgcd9eaj5juvqbi9as49): Failed to open stream: No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 177

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)

Filename: Session/Session.php

Line Number: 137

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once