In vivo and freeze-trapped assays of the energy state of brain and skeletal tissues

Non-invasive, non-destructive assay of energy-related metabolic activity of body tissues is the goal of several biophysical approaches, surface fluorometry of mitochondrial flavoprotein, positron emission tomography and 31 P n.m.r. Each has an appropriate specificity, time range, resolution and tissue damage potential. 31 P n.m.r. is the least invasive and at 72 MHz, with a 20 min averaging time and a 20 mm bore magnet, it affords in vivo assay of energy related compounds of tissues in small animals, such as fish skeletal muscle (loach) and heads of adult mouse and of newborn gerbils. In the transition from normoxia and nitrogen anoxia, decreases of the creatine phosphate : inorganic phosphate ratios from 3.9, 5.0, 2.7 in normoxia to 1.2, 0.04, 0.06 in anoxia occur in fish, mouse and gerbil respectively. The remarkable retention of significant ATP levels (80% of normoxic) in the new-born gerbil through 20 min of N 2 anoxia is clearly demonstrated. Evidence for the origin of much of the in vivo signal from the mouse brain is afforded by the fast freeze-trapping, excision of brain and assay by cryo-n.m.r. (Chance, B. et al . 1978 Proc. natn. Acad. Sci. U.S.A. 75, 4925-4929) at —12 °C, the lowest temperature at which tissue signals are observed.

Polymers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 2348
Author(s):  
Leon Riehakainen ◽  
Chiara Cavallini ◽  
Paolo Armanetti ◽  
Daniele Panetta ◽  
Davide Caramella ◽  
...  

Non-invasive longitudinal imaging of osseointegration of bone implants is essential to ensure a comprehensive, physical and biochemical understanding of the processes related to a successful implant integration and its long-term clinical outcome. This study critically reviews the present imaging techniques that may play a role to assess the initial stability, bone quality and quantity, associated tissue remodelling dependent on implanted material, implantation site (surrounding tissues and placement depth), and biomarkers that may be targeted. An updated list of biodegradable implant materials that have been reported in the literature, from metal, polymer and ceramic categories, is provided with reference to the use of specific imaging modalities (computed tomography, positron emission tomography, ultrasound, photoacoustic and magnetic resonance imaging) suitable for longitudinal and non-invasive imaging in humans. The advantages and disadvantages of the single imaging modality are discussed with a special focus on preclinical imaging for biodegradable implant research. Indeed, the investigation of a new implant commonly requires histological examination, which is invasive and does not allow longitudinal studies, thus requiring a large number of animals for preclinical testing. For this reason, an update of the multimodal and multi-parametric imaging capabilities will be here presented with a specific focus on modern biomaterial research.


2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Martin Thunemann ◽  
Barbara F. Schörg ◽  
Susanne Feil ◽  
Yun Lin ◽  
Jakob Voelkl ◽  
...  

2018 ◽  
Vol 40 (29) ◽  
pp. 2444-2454 ◽  
Author(s):  
Philip D Adamson ◽  
David E Newby

Abstract Non-invasive imaging of the coronary arteries is an enterprise in rapid development. From the research perspective, there is great demand for in vivo techniques that can reliably identify features of high-risk plaque that may offer insight into pathophysiological processes and act as surrogate indicators of response to therapeutic intervention. Meanwhile, there is clear clinical need for greater accuracy in diagnosis and prognostic stratification. Fortunately, ongoing technological improvements and emerging data from randomized clinical trials are helping make these elusive goals a reality. This review provides an update on the current status of non-invasive coronary imaging with computed tomography, magnetic resonance, and positron emission tomography with a focus on current clinical applications and future research directions.


2016 ◽  
Vol 23 (4) ◽  
pp. 496-504 ◽  
Author(s):  
Laura Airas ◽  
Eero Rissanen ◽  
Juha Rinne

Multiple sclerosis (MS) is a complex disease, where several processes can be selected as a target for positron emission topography (PET) imaging. Unlike magnetic resonance imaging (MRI), PET provides specific and quantitative information, and unlike neuropathology, it can be non-invasively applied to living patients, which enables longitudinal follow-up of the MS pathology. In the study of MS, PET can be useful for in vivo evaluation of specific pathological characteristics at various stages of the disease. Increased understanding of the progressive MS pathology will enhance the treatment options of this undertreated condition. The ultimate goal of developing and expanding PET in the study of MS is to have clinical non-invasive in vivo imaging biomarkers of neuroinflammation that will help to establish prognosis and accurately measure response to therapeutics. This topical review provides an overview of the promises and challenges of the use of PET in MS.


2020 ◽  
Vol 93 (1113) ◽  
pp. 20190740 ◽  
Author(s):  
Rong Bing ◽  
Krithika Loganath ◽  
Philip Adamson ◽  
David Newby ◽  
Alastair Moss

Despite recent advances, cardiovascular disease remains the leading cause of death globally. As such, there is a need to optimise our current diagnostic and risk stratification pathways in order to better deliver individualised preventative therapies. Non-invasive imaging of coronary artery plaque can interrogate multiple aspects of coronary atherosclerotic disease, including plaque morphology, anatomy and flow. More recently, disease activity is being assessed to provide mechanistic insights into in vivo atherosclerosis biology. Molecular imaging using positron emission tomography is unique in this field, with the potential to identify specific biological processes using either bespoke or re-purposed radiotracers. This review provides an overview of non-invasive vulnerable plaque detection and molecular imaging of coronary atherosclerosis.


1984 ◽  
Vol 4 (4) ◽  
pp. 610-614 ◽  
Author(s):  
A. Rachman ◽  
L. Kellmann ◽  
J. Krieglstein

The effect of dihydroergocristine on energy metabolism was studied in the isolated perfused rat brain affected by ischemia and in cultivated C-1300 neuroblastoma cells deprived of oxygen and glucose. Creatine phosphate, ATP, ADP, AMP, glucose, glucose-6-phosphate, fructose-6-phosphate, fructose-1,6-diphosphate, pyruvate, and lactate were measured enzymatically. After a perfusion period of 30 min, the cortex of the isolated perfused rat brain exhibited an energy state not different from that in vivo. Dihydroergocristine added to the perfusion medium (5 μmol/L) did not influence these substrate levels under normal perfusion conditions. However, this drug was able to retard the breakdown of high-energy phosphates during ischemia and to accelerate the restoration of the energy state during the postischemic reperfusion period. The perfusion rate was not changed by the drug, and therefore it was assumed that dihydroergocristine could act directly on cell metabolism. This view was supported by the results obtained from experiments using cultivated N-2a neuroblastoma cells. These cells were incubated in a buffered salt solution deprived of glucose and oxygen for 15 min. Under these conditions, dihydroergocristine (2 μmol/L) added to the incubation medium caused changes in the concentrations of the high-energy phosphates similar to those in the isolated brain preparation: It increased the ATP concentration and decreased the ADP concentration significantly.


2022 ◽  
Vol 13 ◽  
Author(s):  
Lei Cao ◽  
Yanyan Kong ◽  
Bin Ji ◽  
Yutong Ren ◽  
Yihui Guan ◽  
...  

The microtubule-associated protein tau (MAPT) plays an important role in Alzheimer’s disease and primary tauopathy diseases. The abnormal accumulation of tau contributes to the development of neurotoxicity, inflammation, neurodegeneration, and cognitive deficits in tauopathy diseases. Tau synergically interacts with amyloid-beta in Alzheimer’s disease leading to detrimental consequence. Thus, tau has been an important target for therapeutics development for Alzheimer’s disease and primary tauopathy diseases. Tauopathy animal models recapitulating the tauopathy such as transgenic, knock-in mouse and rat models have been developed and greatly facilitated the understanding of disease mechanisms. The advance in PET and imaging tracers have enabled non-invasive detection of the accumulation and spread of tau, the associated microglia activation, metabolic, and neurotransmitter receptor alterations in disease animal models. In vivo microPET studies on mouse or rat models of tauopathy have provided significant insights into the phenotypes and time course of pathophysiology of these models and allowed the monitoring of treatment targeting at tau. In this study, we discuss the utilities of PET and recently developed tracers for evaluating the pathophysiology in tauopathy animal models. We point out the outstanding challenges and propose future outlook in visualizing tau-related pathophysiological changes in brain of tauopathy disease animal models.


2021 ◽  
Author(s):  
Ralf Metzner ◽  
Antonia Chlubek ◽  
Jonas Bühler ◽  
Daniel Pflugfelder ◽  
Ulrich Schurr ◽  
...  

Legumes associate with root colonizing rhizobia that provide fixed nitrogen to its plant host in exchange for recently fixed carbon. There is a lack in understanding how individual plants modulate carbon allocation to a nodulated root system as a dynamic response to abiotic stimuli. One reason is that most approaches are based on destructive sampling, making quantification of localized carbon allocation dynamics in the root system difficult. We established an experimental workflow for routinely using non-invasive Positron Emission Tomography (PET) to follow the allocation of leaf-supplied 11C tracer towards individual nodules in a three-dimensional (3D) root system of pea (Pisum sativum). Nitrate was used for triggering the shutdown of biological nitrogen fixation (BNF) expected to rapidly affect carbon allocation dynamics in the root-nodule system. This nitrate treatment lead to a reduction of 11C tracer allocation to nodules by 40% - 47% in 5 treated plants while the variation in control plants was less than 11%. The established experimental pipeline enabled for the first time that several plants could consistently be labelled and measured using 11C tracer in a PET approach to quantify C-allocation to individual nodules following a BNF shutdown. This demonstrates the strength of using 11C tracers in a PET approach for non-invasive quantification of dynamic carbon allocation in several growing plants over several days. A major advantage of the approach is the possibility to investigate carbon dynamics in small regions of interest in a 3D system such as nodules in comparison to whole plant development.


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