monitoring-tumor-metastases-osteolytic-lesions-with-bioluminescence

Monitoring Tumor Metastases and Osteolytic Lesions with Bioluminescence and Micro CT Imaging

Following intracardiac delivery of MDA-MB-231-luc-D3H2LN cells to Nu/Nu mice, systemic metastases developed in the injected animals. Bioluminescence ...

Urinary tract infections (UTIs) are among the most common bacterial infections acquired by humans, particularly in catheterized patients. A major problem with catheterization is the formation of bacterial biofilms on catheter material and the risk of developing persistent UTIs that are difficult to monitor and eradicate. To better understand the course of UTIs and allow more accurate studies of in vivo antibiotic efficacy, we developed a catheter-based biofilm infection model with mice, using bioluminescently engineered bacteria. Two important urinary tract pathogens, Pseudomonas aeruginosa and Proteus mirabilis, were made bioluminescent by stable insertion of a complete lux operon. Segments of catheter material (precolonized or postimplant infected) with either pathogen were placed transurethrally in the lumen of the bladder by using a metal stylet without surgical manipulation. The bioluminescent strains were sufficiently bright to be readily monitored from the outside of infected animals, using a low-light optical imaging system, including the ability to trace the ascending pattern of light-emitting bacteria through ureters to the kidneys. Placement of the catheter in the bladder not only resulted in the development of strong cystitis that persisted significantly longer than in mice challenged with bacterial suspensions alone but also required prolonged antibiotic treatment to reduce the level of infection. Treatment of infected mice for 4 days with ciprofloxacin at 30 mg/kg of body weight twice a day cured cystitis and renal infection in noncatheterized mice. Similarly, ciprofloxacin reduced the bacterial burden to undetectable levels in catheterized mice but did not inhibit rebound of the infection upon cessation of antibiotic therapy. This methodology easily allows spatial information to be monitored sequentially throughout the entire disease process, including ascending UTI, treatment efficacy, and relapse, all without exogenous sampling, which is not possible with conventional methods.

Noninvasive biophotonic imaging for monitoring of catheter-associated urinary tract infections and therapy in mice.

Nichtinvasive Bildgebung Biophotonik f&#xFC;r die &#xDC;berwachung von Katheter-assoziierten Infektionen der Harnwege und Therapie bei M&#xE4;usen.

Noninvasive real-time in vivo bioluminescent imaging was used to assess the spread of Streptococcus pneumoniae throughout the spinal cord and brain during the acute stages of bacterial meningitis. A mouse model was established by lumbar (LP) or intracisternal (IC) injection of bioluminescent S. pneumoniae into the subarachnoid space. Bacteria replicated initially at the site of inoculation and spread progressively from the spinal cord to the brain or from the brain down to the cervical part of the spinal column and to the lower vertebral levels. After 24 hr, animals showed strong bioluminescent signals throughout the spinal canal, indicating acute meningitis of the intracranial and intraspinal meninges. A decline in bacterial cell viability, as judged by a reduction in the bioluminescent signal, was observed over time in animals treated with ceftriaxone, but not in untreated groups. Mice treated with the antibiotic survived infection, whereas all mice in untreated groups became moribund, first in the IC group then in the LP group. No untreated animal survived beyond 48 hr after induction of infection. Colony counts of infected cerebrospinal fluid (CSF) correlated positively with bioluminescent signals. This methodology is especially appealing because it allows detecting infected mice as early as 3 hr after inoculation, provide temporal, sequential, and spatial distribution of bacteria within the brain and spinal cord throughout the entire disease process and the rapid monitoring of treatment efficacy in a nondestructive manner. Moreover, it avoids the need to sacrifice the animals for CSF sampling and the potential manipulative damage that can occur with other conventional methods.

Noninvasive monitoring of pneumococcal meningitis and evaluation of treatment efficacy in an experimental mouse model.

Nichtinvasive &#xDC;berwachung des Pneumokokken-Meningitis und Auswertung der Wirksamkeit der Behandlung in einem experimentellen Mausmodell.

We developed a method for simultaneous in vivo biophotonic monitoring of pneumococcal meningitis and the accompanying neuronal injury in live transgenic mice. Streptococcus pneumoniae engineered for bioluminescence (lux) was used for direct visualization of disease progression and antibiotic treatment in a mouse model of meningitis. The host response was monitored in transgenic mice containing an inducible firefly luciferase (luc) reporter gene under transcriptional control of the mouse glial fibrillary acidic protein (GFAP) promoter. Based on the different spectra of light emission and substrate requirements for lux and luc, we were able to separately monitor the two reporters using a highly sensitive in vivo imaging system. The level of neuronal damage and recovery following antibiotic treatment was dependent on the time of treatment. This model has potential for simultaneous multiparameter monitoring and testing of therapies that target the pathogen or host response to prevent neuronal injury and recovery.

Reduction of astrogliosis by early treatment of pneumococcal meningitis measured by simultaneous imaging, in vivo, of the pathogen and host response.

Wir entwickelten eine Methode zur gleichzeitigen in-vivo Biophotonische &Uuml;berwachung der Pneumokokken-Meningitis und die begleitenden neuronalen Verletzung in transgenen M&auml;usen Leben. Pneumokokken, die speziell f&uuml;r die Biolumineszenz (Lux) wurde f&uuml;r direkte Visualisierung der Progression und Antibiotikum Behandlung in einem Mausmodell der Meningitis verwendet. Die Host-Reaktion wurde in transgenen M&auml;usen, enth&auml;lt ein durch Induktion Gl&uuml;hw&uuml;rmchen Luciferase (Luc) Reporter-gen unter transkriptionelle Kontrolle des Projekttr&auml;gers Maus Gliazellen fibrill&auml;re sauren Protein (GFAP) &uuml;berwacht. Auf der Grundlage der verschiedenen Spektren der Lichtemission und Substrat Anforderungen f&uuml;r Lux und Luc, konnten wir die zwei Reporter, die mit einem hochempfindlichen in-vivo-imaging-System separat zu &uuml;berwachen. Neuronale Sch&auml;den und Recovery nach Antibiotika-Behandlung war die Zeit der Behandlung abh&auml;ngig. Dieses Modell hat Potenzial f&uuml;r gleichzeitige Multiparameter &Uuml;berwachung und Pr&uuml;fung von Therapien, die gezielt die Erreger oder Host-Antwort, um neuronale Sch&auml;digung und Wiederherstellung zu verhindern.

Reduzierung der Astrogliosis durch fr&uuml;hzeitige Behandlung von Pneumokokken Meningitis durch gleichzeitige imaging, in-vivo, die Erreger und Host-Reaktion gemessen.

Article	Year
Noninvasive biophotonic imaging for monitoring of catheter-associated urinary tract infections and therapy in mice. Infection and immunity\| PubMed ID: 15972473	2005
Noninvasive monitoring of pneumococcal meningitis and evaluation of treatment efficacy in an experimental mouse model. Molecular imaging\| PubMed ID: 16105511	2005
Reduction of astrogliosis by early treatment of pneumococcal meningitis measured by simultaneous imaging, in vivo, of the pathogen and host response. Infection and immunity\| PubMed ID: 16299273	2005

Kshitij Modi

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