Sparse Reconstruction for Bioluminescence Tomography Based on the Semigreedy Method

Bioluminescence tomography (BLT) is a molecular imaging modality which can three-dimensionally resolve the molecular processes in small animalsin vivo. The ill-posedness nature of BLT problem makes its reconstruction bears nonunique solution and is sensitive to noise. In this paper, we proposed a sparse BLT reconstruction algorithm based on semigreedy method. To reduce the ill-posedness and computational cost, the optimal permissible source region was automatically chosen by using an iterative search tree. The proposed method obtained fast and stable source reconstruction from the whole body and imposed constraint without using a regularization penalty term. Numerical simulations on a mouse atlas, andin vivomouse experiments were conducted to validate the effectiveness and potential of the method.

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Source reconstruction for bioluminescence tomography via L1∕2 regularization

Journal of Innovative Optical Health Sciences ◽

10.1142/s1793545817500146 ◽

2018 ◽

Vol 11 (02) ◽

pp. 1750014 ◽

Cited By ~ 1

Author(s):

Jingjing Yu ◽

Qiyue Li ◽

Haiyu Wang

Keyword(s):

Image Quality ◽

Matching Pursuit ◽

Imaging Modality ◽

Reconstruction Algorithm ◽

Reconstruction Method ◽

Reconstruction Algorithms ◽

Preclinical Research ◽

Bioluminescence Tomography ◽

Comparison Results ◽

Stable Reconstruction

Bioluminescence tomography (BLT) is an important noninvasive optical molecular imaging modality in preclinical research. To improve the image quality, reconstruction algorithms have to deal with the inherent ill-posedness of BLT inverse problem. The sparse characteristic of bioluminescent sources in spatial distribution has been widely explored in BLT and many L1-regularized methods have been investigated due to the sparsity-inducing properties of L1 norm. In this paper, we present a reconstruction method based on L[Formula: see text] regularization to enhance sparsity of BLT solution and solve the nonconvex L[Formula: see text] norm problem by converting it to a series of weighted L1 homotopy minimization problems with iteratively updated weights. To assess the performance of the proposed reconstruction algorithm, simulations on a heterogeneous mouse model are designed to compare it with three representative sparse reconstruction algorithms, including the weighted interior-point, L1 homotopy, and the Stagewise Orthogonal Matching Pursuit algorithm. Simulation results show that the proposed method yield stable reconstruction results under different noise levels. Quantitative comparison results demonstrate that the proposed algorithm outperforms the competitor algorithms in location accuracy, multiple-source resolving and image quality.

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Identify. Quantify. Predict. Why Immunologists Should Widely Use Molecular Imaging for Coronavirus Disease 2019

Frontiers in Immunology ◽

10.3389/fimmu.2021.568959 ◽

2021 ◽

Vol 12 ◽

Author(s):

Freimut D. Juengling ◽

Antonio Maldonado ◽

Frank Wuest ◽

Thomas H. Schindler

Keyword(s):

Molecular Imaging ◽

Current Knowledge ◽

Imaging Modality ◽

Acute Infection ◽

Molecular Probes ◽

Whole Body ◽

Prognostic Indicators ◽

Imaging Biomarkers ◽

Body Scale

Molecular imaging using PET/CT or PET/MRI has evolved from an experimental imaging modality at its inception in 1972 to an integral component of diagnostic procedures in oncology, and, to lesser extent, in cardiology and neurology, by successfully offering in-vivo imaging and quantitation of key pathophysiological targets or molecular signatures, such as glucose metabolism in cancerous disease. Apart from metabolism probes, novel radiolabeled peptide and antibody PET tracers, including radiolabeled monoclonal antibodies (mAbs) have entered the clinical arena, providing the in-vivo capability to collect target-specific quantitative in-vivo data on cellular and molecular pathomechanisms on a whole-body scale, and eventually, extract imaging biomarkers possibly serving as prognostic indicators. The success of molecular imaging in mapping disease severity on a whole-body scale, and directing targeted therapies in oncology possibly could translate to the management of Coronavirus Disease 2019 (COVID-19), by identifying, localizing, and quantifying involvement of different immune mediated responses to the infection with SARS-COV2 during the course of acute infection and possible, chronic courses with long-term effects on specific organs. The authors summarize current knowledge for medical imaging in COVID-19 in general with a focus on molecular imaging technology and provide a perspective for immunologists interested in molecular imaging research using validated and immediately available molecular probes, as well as possible future targets, highlighting key targets for tailored treatment approaches as brought up by key opinion leaders.

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Ultrafast Doppler Reveals the Mapping of Cerebral Vascular Resistivity in Neonates

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2014.49 ◽

2014 ◽

Vol 34 (6) ◽

pp. 1009-1017 ◽

Cited By ~ 36

Author(s):

Charlie Demené ◽

Mathieu Pernot ◽

Valérie Biran ◽

Marianne Alison ◽

Mathias Fink ◽

...

Keyword(s):

Imaging Modality ◽

High Sensitivity ◽

Frame Rate ◽

Doppler Imaging ◽

Whole Body ◽

Simultaneous Estimation ◽

Wide Field ◽

Whole Body Cooling ◽

2D Resistivity

In vivo mapping of the full vasculature dynamics based on Ultrafast Doppler is showed noninvasively in the challenging case of the neonatal brain. Contrary to conventional pulsed-wave (PW) Doppler Ultrasound limited for >40 years to the estimation of vascular indices at a single location, the ultrafast frame rate (5,000 Hz) obtained using plane-wave transmissions leads to simultaneous estimation of full Doppler spectra in all pixels of wide field-of-view images within a single cardiac cycle and high sensitivity Doppler imaging. Consequently, 2D quantitative maps of the cerebro-vascular resistivity index (RI) are processed and found in agreement with local measurements obtained on large arteries of healthy neonates using conventional PW Doppler. Changes in 2D resistivity maps are monitored during recovery after therapeutic whole-body cooling of full-term neonates treated for hypoxic ischemic encephalopathy. Arterial and venous vessels are unambiguously differentiated on the basis of their distinct hemodynamics. The high spatial (250 × 250 μm2) and temporal resolution (<1 ms) of Ultrafast Doppler imaging combined with deep tissue penetration enable precise quantitative mapping of deep brain vascular dynamics and RI, which is far beyond the capabilities of any other imaging modality.

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Quantitative Ranking of Ligand Binding Kinetics with a Multiscale Milestoning Simulation Approach

10.26434/chemrxiv.6726977.v1 ◽

2018 ◽

Author(s):

Benjamin R. Jagger ◽

Christoper T. Lee ◽

Rommie Amaro

Keyword(s):

Molecular Dynamics ◽

Drug Discovery ◽

Small Molecule ◽

Brownian Dynamics ◽

Model Simulation ◽

Computational Cost ◽

Lead Selection ◽

Delta G ◽

Dynamics Simulations

<p>The ranking of small molecule binders by their kinetic (kon and koff) and thermodynamic (delta G) properties can be a valuable metric for lead selection and optimization in a drug discovery campaign, as these quantities are often indicators of in vivo efficacy. Efficient and accurate predictions of these quantities can aid the in drug discovery effort, acting as a screening step. We have previously described a hybrid molecular dynamics, Brownian dynamics, and milestoning model, Simulation Enabled Estimation of Kinetic Rates (SEEKR), that can predict kon’s, koff’s, and G’s. Here we demonstrate the effectiveness of this approach for ranking a series of seven small molecule compounds for the model system, -cyclodextrin, based on predicted kon’s and koff’s. We compare our results using SEEKR to experimentally determined rates as well as rates calculated using long-timescale molecular dynamics simulations and show that SEEKR can effectively rank the compounds by koff and G with reduced computational cost. We also provide a discussion of convergence properties and sensitivities of calculations with SEEKR to establish “best practices” for its future use.</p>

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OP0178 IMAGING NEOANGIOGENESIS IN RHEUMATOID ARTHRITIS (INIRA): WHOLE-BODY SYNOVIAL UPTAKE OF A 99MTC-LABELLED RGD PEPTIDE IS HIGHLY CORRELATED WITH POWER DOPPLER ULTRASOUND

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5482 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 110.2-111

Author(s):

L. Attipoe ◽

S. Subesinghe ◽

C. Blanco-Gil ◽

M. Opena ◽

M. Rosser ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Correlation Coefficient ◽

Doppler Ultrasound ◽

Imaging Modality ◽

Power Doppler ◽

Whole Body ◽

Total Power ◽

Acquisition Time ◽

Power Doppler Ultrasound ◽

Highly Correlated

Background:Power Doppler ultrasound (PDUS) is superior to clinical examination in detecting synovitis in patients with rheumatoid arthritis (RA). Although dynamic and cheap it is impractical to scan large numbers of joints in routine clinical settings. MRI, whilst sensitive for synovitis, is expensive and routine use is limited to targeted joints. Bone scintigraphy produces whole body images but due to limited specificity is not routinely used.99mTc-maraciclatide (Serac Healthcare) is a radiolabelled tracer which binds with high affinity to integrin αvβ3, a cell-adhesion molecule up-regulated on neoangiogenic blood vessels. It therefore has the potential to image synovial inflammation at the whole-body level. We previously showed in a pilot study that uptake was seen in the inflamed joints of five RA patients and that this correlated with PDUS. This study explores correlation with PDUS in a larger groups of patients with varied disease activity.Objectives:To determine the correlation between ultrasound and99mTc-maraciclatide imaging in patients with rheumatoid arthritis.Methods:50 patients with RA fulfilling ACR 2010 classification criteria were recruited. Patients underwent an ultrasound scan of 40 joints with grey scale (GS) and PD quantification. Each joint was scored on a scale of 0-3 for GS and PD with a total score calculated for each patient. Within 3 hours of the ultrasound patients were injected with 740 MBq of99mTc-maraciclatide. Using a gamma camera, whole body planar views and dedicated hand and foot views were taken 2 hours after injection (Figure 1). Acquisition time was 20 minutes for whole body and 20 minutes for hand and foot views.99mTc-maraciclatide images were scored as positive or negative uptake for each joint (binary score). A quantitative score was also calculated for each joint where there was uptake with this corrected for background uptake. Total binary and quantitative scores per patient were calculated.Ultrasound and99mTc-maraciclatide scores were tested for correlation with Pearson’s correlation coefficient (r). Interrater agreement for 2 scorers was calculated using kappa (ĸ) and concordance correlation coefficient (Pc).Results:Strong correlation was seen when total PDUS was compared to binary scores (r=0.92, r2=0.85) (Figure 2) and quantitative scores (r=0.85, r2=0.72). ĸ was 0.82 and 0.79 for binary and ultrasound scores respectively.Pcwas 0.82 for quantitative scores. p was <0.0005 for all results.99mTc-maraciclatide uptake was also seen in inflamed tendons/tendon sheaths. The imaging procedure was well-tolerated. There were no tracer-related adverse events.Figure 1.99mTc-maraciclatide imaging with dedicated hand and foot viewsConclusion:99mTc-maraciclatide uptake was highly correlated with PDUS highlighting its potential as an alternative imaging modality.99mTc-based planar imaging has the unique capacity to image the whole body and hence the total synovial inflammatory load in a quick acquisition. The imaging equipment to perform these scans is already widely available in radiology departments. Interpretation of scans is also much simpler compared to US/MRI. It could therefore have a role in key decision-making points in pathways for diagnosis, treatment failure, and remission prior to dose tapering.Figure 2.Correlation between total power doppler and99mTc-maraciclatide binary scoresDisclosure of Interests:None declared

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Use of Toxicokinetics in Risk Assessment Based on In Vitro Data

Alternatives to Laboratory Animals ◽

10.1177/026119299302100209 ◽

1993 ◽

Vol 21 (2) ◽

pp. 173-180

Author(s):

Gunnar Johanson

Keyword(s):

Risk Assessment ◽

Whole Body ◽

External Exposure ◽

Target Dose ◽

Toxic Response ◽

Route Of Exposure ◽

Vitro Data ◽

In Vitro Data

This presentation addresses some aspects of the methodology, advantages and problems associated with toxicokinetic modelling based on in vitro data. By using toxicokinetic models, particularly physiologically-based ones, it is possible, in principle, to describe whole body toxicokinetics, target doses and toxic effects from in vitro data. Modelling can be divided into three major steps: 1) to relate external exposure (applied dose) of xenobiotic to target dose; 2) to establish the relationship between target dose and effect (in vitro data, e.g. metabolism in microsomes, partitioning in tissue homogenates, and toxicity in cell cultures, are useful in both steps); and 3) to relate external exposure to toxic effect by combining the first two steps. Extrapolations from in vitro to in vivo, between animal and man, and between high and low doses, can easily be carried out by toxicokinetic simulations. In addition, several factors that may affect the toxic response by changing the target dose, such as route of exposure and physical activity, can be studied. New insights concerning the processes involved in toxicity often emerge during the design, refinement and validation of the model. The modelling approach is illustrated by two examples: 1) the carcinogenicity of 1,3-butadiene; and 2) the haematotoxicity of 2-butoxyethanol. Toxicokinetic modelling is an important tool in toxicological risk assessment based on in vitro data. Many factors, some of which can, and should be, studied in vitro, are involved in the expression of toxicity. Successful modelling depends on the identification and quantification of these factors.

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Adipocyte PHLPP2 inhibition prevents obesity-induced fatty liver

Nature Communications ◽

10.1038/s41467-021-22106-2 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

KyeongJin Kim ◽

Jin Ku Kang ◽

Young Hoon Jung ◽

Sang Bae Lee ◽

Raffaela Rametta ◽

...

Keyword(s):

Fatty Liver ◽

Whole Body ◽

Acid Oxidation ◽

Chow Diet ◽

Peroxisome Proliferator ◽

Obese Mice ◽

Ph Domain ◽

Peroxisome Proliferator Activated Receptor

AbstractIncreased adiposity confers risk for systemic insulin resistance and type 2 diabetes (T2D), but mechanisms underlying this pathogenic inter-organ crosstalk are incompletely understood. We find PHLPP2 (PH domain and leucine rich repeat protein phosphatase 2), recently identified as the Akt Ser473 phosphatase, to be increased in adipocytes from obese mice. To identify the functional consequence of increased adipocyte PHLPP2 in obese mice, we generated adipocyte-specific PHLPP2 knockout (A-PHLPP2) mice. A-PHLPP2 mice show normal adiposity and glucose metabolism when fed a normal chow diet, but reduced adiposity and improved whole-body glucose tolerance as compared to Cre- controls with high-fat diet (HFD) feeding. Notably, HFD-fed A-PHLPP2 mice show increased HSL phosphorylation, leading to increased lipolysis in vitro and in vivo. Mobilized adipocyte fatty acids are oxidized, leading to increased peroxisome proliferator-activated receptor alpha (PPARα)-dependent adiponectin secretion, which in turn increases hepatic fatty acid oxidation to ameliorate obesity-induced fatty liver. Consistently, adipose PHLPP2 expression is negatively correlated with serum adiponectin levels in obese humans. Overall, these data implicate an adipocyte PHLPP2-HSL-PPARα signaling axis to regulate systemic glucose and lipid homeostasis, and suggest that excess adipocyte PHLPP2 explains decreased adiponectin secretion and downstream metabolic consequence in obesity.

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The Hemostatic Effect of 51Cr-Labelled Platelets

10.1055/s-0039-1689680 ◽

1975 ◽

Author(s):

J. Björnson ◽

I. Aursnes

Keyword(s):

Whole Body ◽

Platelet Concentrates ◽

Platelet Aggregability ◽

Hemostatic Effect ◽

Normal Platelet ◽

Labelling Procedure

In the interpretation of data obtained with 51Cr-labelled platelets it is vital to know whether they are functionally normal. Although survival of 51Cr-labelled platelets in vivo appears to be normal, platelet aggregability- has recently been shown to be reduced after the labelling procedure (Björnson, J., Sc and. J. Haemat. 13, 252–259).The aim of the present study was to examine the hemostatic effect of labelled platelets. Rabbits were made thrombocytopenic (< 35,000/μ1) by whole body irradiation. Bleeding times were recorded after standardized cuts on the inner side of the ear, a method showing an acceptable reproducibility (< 3 min in normals). The animals were then transfused with labelled platelet concentrates, increasing the platelet levels to about 200,000/μ) blood. Bleeding times of more than 15 min before transfusion were almost normalized 1 and 4 hours after transfusion. In controls transfusion of PRP led to similar shortening of bleeing time.It is concluded that platelets subjected to the 51Cr-labelling procedure to a large extent retain their hemostatic ability.

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In Vivo Imaging of Biodegradable Implants and Related Tissue Biomarkers

Polymers ◽

10.3390/polym13142348 ◽

2021 ◽

Vol 13 (14) ◽

pp. 2348

Author(s):

Leon Riehakainen ◽

Chiara Cavallini ◽

Paolo Armanetti ◽

Daniele Panetta ◽

Davide Caramella ◽

...

Keyword(s):

Imaging Modality ◽

Imaging Techniques ◽

Special Focus ◽

Tissue Remodelling ◽

Biodegradable Implant ◽

Advantages And Disadvantages ◽

Non Invasive ◽

Positron Emission ◽

Longitudinal Imaging

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.

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IMMU-31. QUANTITATIVE EVALUATION OF ROUTES OF ADMINISTRATION OF IMMUNOTHERAPEUTIC T CELLS TO ORTHOTOPIC GLIOMA

Neuro-Oncology ◽

10.1093/neuonc/noaa215.461 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii111-ii111

Author(s):

Lan Hoang-Minh ◽

Angelie Rivera-Rodriguez ◽

Fernanda Pohl-Guimarães ◽

Seth Currlin ◽

Christina Von Roemeling ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Tumor Growth ◽

Ex Vivo ◽

Adoptive T Cell Therapy ◽

Whole Body ◽

T Cell Therapy ◽

Clinical Responses

Abstract SIGNIFICANCE Adoptive T cell therapy (ACT) has emerged as the most effective treatment against advanced malignant melanoma, eliciting remarkable objective clinical responses in up to 75% of patients with refractory metastatic disease, including within the central nervous system. Immunologic surrogate endpoints correlating with treatment outcome have been identified in these patients, with clinical responses being dependent on the migration of transferred T cells to sites of tumor growth. OBJECTIVE We investigated the biodistribution of intravenously or intraventricularly administered T cells in a murine model of glioblastoma at whole body, organ, and cellular levels. METHODS gp100-specific T cells were isolated from the spleens of pmel DsRed transgenic C57BL/6 mice and injected intravenously or intraventricularly, after in vitro expansion and activation, in murine KR158B-Luc-gp100 glioma-bearing mice. To determine transferred T cell spatial distribution, the brain, lymph nodes, heart, lungs, spleen, liver, and kidneys of mice were processed for 3D imaging using light-sheet and multiphoton imaging. ACT T cell quantification in various organs was performed ex vivo using flow cytometry, 2D optical imaging (IVIS), and magnetic particle imaging (MPI) after ferucarbotran nanoparticle transfection of T cells. T cell biodistribution was also assessed in vivo using MPI. RESULTS Following T cell intravenous injection, the spleen, liver, and lungs accounted for more than 90% of transferred T cells; the proportion of DsRed T cells in the brains was found to be very low, hovering below 1%. In contrast, most ACT T cells persisted in the tumor-bearing brains following intraventricular injections. ACT T cells mostly concentrated at the periphery of tumor masses and in proximity to blood vessels. CONCLUSIONS The success of ACT immunotherapy for brain tumors requires optimization of delivery route, dosing regimen, and enhancement of tumor-specific lymphocyte trafficking and effector functions to achieve maximal penetration and persistence at sites of invasive tumor growth.

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