Rapid T1rho dispersion imaging for improved characterization of myocardial tissue using synthetic dispersion reconstruction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Gram ◽  
D Gensler ◽  
P Winter ◽  
M Seethaler ◽  
P.M Jakob ◽  
...  

Abstract Introduction Over the past decade, CMRI has become the method of choice for characterizing fibrotic scars. Native T1ρ mapping offers an alternative to conventional T1 and T2 quantification techniques due to its high sensitivity to low-frequency processes. In addition, there is the possibility of T1ρ dispersion imaging, which could be used as a sensitive biomarker for assessing myocardial fibrosis [1]. However, due to a very long measurement time, T1ρ dispersion quantification in myocardium can hardly be done in the limited time of a small animal study. In this work we present a concept for rapid T1ρ dispersion quantification based on the new approach of synthetic dispersion reconstruction (SynDR). Theory A T1ρ map is calculated by measuring Nt T1ρ weighted images using different spin lock (SL) times. T1ρ dispersion quantification requires Nf T1ρ maps with different SL amplitudes. Hence the measurement time is very time consuming, because it requires the acquisition of Nt*Nf images (full mapping). With our new approach (SynDR), only a single T1ρ reference map and a series of dispersion weighted images need to be acquired. The T1ρ dispersion can be reconstructed by synthetically generated maps, whereby each map is calculated from the reference map and the dispersion weighted images, only requiring Nt+Nf images. Methods All measurements were performed on a 7T small animal scanner. The method was based on an optional cartesian/radial gradient echo sequence using large flip angles (45°) and an optimized readout sorting. The quantification accuracy of SynDR was compared with full mapping measurements in a phantom experiment and validated in vivo on mice. The synthetic T1ρ maps were used to perform a dispersion analysis in myocardium. Results The comparison between SynDR and the full mapping reference in phantoms showed a very high quantification accuracy with a mean/maximum deviation of 1.1% and 1.7%. Fig. 1 shows synthetic T1ρ maps (a) in healthy mice and the obtained dispersion map (b) using SynDR. In the dispersion analysis (c) a T1ρ slope of 5.6±1.5ms/kHz was obtained for myocardium. Here an acceleration factor of 4 could be realized in comparison to full mapping. In further measurements, an acceleration of 7.4 could be reached using a radial readout with KWIC filter view sharing. Discussion In this work, a novel T1ρ dispersion imaging method was presented that far exceeds the speed of conventional full mapping methods. The acceleration is based on avoiding unnecessary measurements of T1ρ weighted images through more efficient mathematical modeling. Further acceleration could be achieved using an optimized radial data acquisition. The method shows good image quality and high quantification accuracy both in phantom and in vivo. Based on the promising results, further studies in mice are planned to investigate the dispersion character of healthy and diseased tissues. Reference [1] Yin Q et al. Magn Reson Imaging. 2017 Oct; 42:69–73. SynDR method and T1ρ dispersion analysis Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): BRD, Bundesministerium für Bildung und Forschung

Author(s):  
Maximilian Gram ◽  
Daniel Gensler ◽  
Patrick Winter ◽  
Michael Seethaler ◽  
Paula Anahi Arias-Loza ◽  
...  

Abstract Purpose T1ρ dispersion quantification can potentially be used as a cardiac magnetic resonance index for sensitive detection of myocardial fibrosis without the need of contrast agents. However, dispersion quantification is still a major challenge, because T1ρ mapping for different spin lock amplitudes is a very time consuming process. This study aims to develop a fast and accurate T1ρ mapping sequence, which paves the way to cardiac T1ρ dispersion quantification within the limited measurement time of an in vivo study in small animals. Methods A radial spin lock sequence was developed using a Bloch simulation-optimized sampling pattern and a view-sharing method for image reconstruction. For validation, phantom measurements with a conventional sampling pattern and a gold standard sequence were compared to examine T1ρ quantification accuracy. The in vivo validation of T1ρ mapping was performed in N = 10 mice and in a reproduction study in a single animal, in which ten maps were acquired in direct succession. Finally, the feasibility of myocardial dispersion quantification was tested in one animal. Results The Bloch simulation-based sampling shows considerably higher image quality as well as improved T1ρ quantification accuracy (+ 56%) and precision (+ 49%) compared to conventional sampling. Compared to the gold standard sequence, a mean deviation of − 0.46 ± 1.84% was observed. The in vivo measurements proved high reproducibility of myocardial T1ρ mapping. The mean T1ρ in the left ventricle was 39.5 ± 1.2 ms for different animals and the maximum deviation was 2.1% in the successive measurements. The myocardial T1ρ dispersion slope, which was measured for the first time in one animal, could be determined to be 4.76 ± 0.23 ms/kHz. Conclusion This new and fast T1ρ quantification technique enables high-resolution myocardial T1ρ mapping and even dispersion quantification within the limited time of an in vivo study and could, therefore, be a reliable tool for improved tissue characterization.


Sensors ◽  
2021 ◽  
Vol 21 (1) ◽  
pp. 283
Author(s):  
Rianne Bulsink ◽  
Mithun Kuniyil Ajith Singh ◽  
Marvin Xavierselvan ◽  
Srivalleesha Mallidi ◽  
Wiendelt Steenbergen ◽  
...  

Oxygen saturation imaging has potential in several preclinical and clinical applications. Dual-wavelength LED array-based photoacoustic oxygen saturation imaging can be an affordable solution in this case. For the translation of this technology, there is a need to improve its accuracy and validate it against ground truth methods. We propose a fluence compensated oxygen saturation imaging method, utilizing structural information from the ultrasound image, and prior knowledge of the optical properties of the tissue with a Monte-Carlo based light propagation model for the dual-wavelength LED array configuration. We then validate the proposed method with oximeter measurements in tissue-mimicking phantoms. Further, we demonstrate in vivo imaging on small animal and a human subject. We conclude that the proposed oxygen saturation imaging can be used to image tissue at a depth of 6–8 mm in both preclinical and clinical applications.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jiang Lan Fan ◽  
Jose A. Rivera ◽  
Wei Sun ◽  
John Peterson ◽  
Henry Haeberle ◽  
...  

AbstractUnderstanding the structure and function of vasculature in the brain requires us to monitor distributed hemodynamics at high spatial and temporal resolution in three-dimensional (3D) volumes in vivo. Currently, a volumetric vasculature imaging method with sub-capillary spatial resolution and blood flow-resolving speed is lacking. Here, using two-photon laser scanning microscopy (TPLSM) with an axially extended Bessel focus, we capture volumetric hemodynamics in the awake mouse brain at a spatiotemporal resolution sufficient for measuring capillary size and blood flow. With Bessel TPLSM, the fluorescence signal of a vessel becomes proportional to its size, which enables convenient intensity-based analysis of vessel dilation and constriction dynamics in large volumes. We observe entrainment of vasodilation and vasoconstriction with pupil diameter and measure 3D blood flow at 99 volumes/second. Demonstrating high-throughput monitoring of hemodynamics in the awake brain, we expect Bessel TPLSM to make broad impacts on neurovasculature research.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 977.1-977
Author(s):  
A. Potapova ◽  
O. Egorova ◽  
O. Alekseeva ◽  
A. Volkov ◽  
S. Radenska-Lopovok

Background:Ultrasound (US) is a non-invasive and safe imaging method that allows in vivo differentiation of the morphological structures of subcutaneous fat (SCF) tissue in in normal and pathology.Objectives:Reveal features of ultrasound changes in SCF in panniculitis (Pn).Methods:57 patients (f – 45, m - 12) aged 18 - 67 years with an initial diagnosis of erythema nodosum and a disease duration of 3.6 ± 1.4 years were examined. In addition to the general clinical examination, a computed tomography of the chest organs and a pathomorphological examination of a skin biopsy from the site of the node were performed. Ultrasound was performed on a MyLabTwice apparatus (ESAOTE, Italy) using a multi-frequency linear transducer (10-18 MHz) with the PD technique, the parameters of which were adapted for recording low-speed flows (PRF 300-600 Hz, low filter, dynamic range - 20-40 dB), the presence of vascularization was assessed not only in the affected area, but also on the contralateral side using high-energy Doppler.Results:33 patients were diagnosed with septal Pn (SPn), 24 - lobular Pn (LPn). In all cases, the diagnosis was verified by histological examination. Ultrasound made it possible to assess the thickness, echoicity and vascularization of the SCF. In 35 patients, significant thickening of the SCF was revealed (as compared to the contralateral side), of which in 14 cases with SPn, in 21 - with LPn. Significant diffuse thickening of the SCF with the contralateral side was observed in 18 patients, incl. in 12 (66%) patients with LPn. Limited thickening was more typical for SPn (73%). A significant increase in the echoicity of the SCF was noted in all forms of Pn. A “lobular” echo pattern with an anechogenic environment was observed in 25 patients, of which 18 (72%) had LPn. An increase in vascularization compared to the contralateral side was recorded in 30 cases (SPn-17, LPn-13).Conclusion:The obtained preliminary results indicate the important role of ultrasound in assessing the depth and prevalence of the inflammatory process at Pn. To clarify the diagnostic value of this method, further studies are needed on a larger sample of patients.Disclosure of Interests:None declared


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Henriette Frikke-Schmidt ◽  
Peter Arvan ◽  
Randy J. Seeley ◽  
Corentin Cras-Méneur

AbstractWhile numerous techniques can be used to measure and analyze insulin secretion in isolated islets in culture, assessments of insulin secretion in vivo are typically indirect and only semiquantitative. The CpepSfGFP reporter mouse line allows the in vivo imaging of insulin secretion from individual islets after a glucose stimulation, in live, anesthetized mice. Imaging the whole pancreas at high resolution in live mice to track the response of each individual islet over time includes numerous technical challenges and previous reports were only limited in scope and non-quantitative. Elaborating on this previous model—through the development of an improved methodology addressing anesthesia, temperature control and motion blur—we were able to track and quantify longitudinally insulin content throughout a glucose challenge in up to two hundred individual islets simultaneously. Through this approach we demonstrate quantitatively for the first time that while isolated islets respond homogeneously to glucose in culture, their profiles differ significantly in vivo. Independent of size or location, some islets respond sharply to a glucose stimulation while others barely secrete at all. This platform therefore provides a powerful approach to study the impact of disease, diet, surgery or pharmacological treatments on insulin secretion in the intact pancreas in vivo.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Morten E. Pedersen ◽  
Ragna M. S. Haegebaert ◽  
Jesper Østergaard ◽  
Henrik Jensen

AbstractThe understanding and characterization of protein interactions is crucial for elucidation of complicated biomolecular processes as well as for the development of new biopharmaceutical therapies. Often, protein interactions involve multiple binding, avidity, oligomerization, and are dependent on the local environment. Current analytical methodologies are unable to provide a detailed mechanistic characterization considering all these parameters, since they often rely on surface immobilization, cannot measure under biorelevant conditions, or do not feature a structurally-related readout for indicating formation of multiple bound species. In this work, we report the use of flow induced dispersion analysis (FIDA) for in-solution characterization of complex protein interactions under in vivo like conditions. FIDA is an immobilization-free ligand binding methodology employing Taylor dispersion analysis for measuring the hydrodynamic radius (size) of biomolecular complexes. Here, the FIDA technology is utilized for a size-based characterization of the interaction between TNF-α and adalimumab. We report concentration-dependent complex sizes, binding affinities (Kd), kinetics, and higher order stoichiometries, thus providing essential information on the TNF-α–adalimumab binding mechanism. Furthermore, it is shown that the avidity stabilized complexes involving formation of multiple non-covalent bonds are formed on a longer timescale than the primary complexes formed in a simple 1 to 1 binding event.


2019 ◽  
Vol 12 (06) ◽  
pp. 1950012 ◽  
Author(s):  
Hequn Zhang ◽  
Weisi Xie ◽  
Ming Chen ◽  
Liang Zhu ◽  
Zhe Feng ◽  
...  

Rodents are popular biological models for physiological and behavioral research in neuroscience and rats are better models than mice due to their higher genome similarity to human and more accessible surgical procedures. However, rat brain is larger than mice brain and it needs powerful imaging tools to implement better penetration against the scattering of the thicker brain tissue. Three-photon fluorescence microscopy (3PFM) combined with near-infrared (NIR) excitation has great potentials for brain circuits imaging because of its abilities of anti-scattering, deep-tissue imaging, and high signal-to-noise ratio (SNR). In this work, a type of AIE luminogen with red fluorescence was synthesized and encapsulated with Pluronic F-127 to make up form nanoparticles (NPs). Bright DCDPP-2TPA NPs were employed for in vivo three-photon fluorescent laser scanning microscopy of blood vessels in rats brain under 1550[Formula: see text]nm femtosecond laser excitation. A fine three-dimensional (3D) reconstruction up to the deepness of 600[Formula: see text][Formula: see text]m was achieved and the blood flow velocity of a selected vessel was measured in vivo as well. Our 3PFM deep brain imaging method simultaneously recorded the morphology and function of the brain blood vessels in vivo in the rat model. Using this angiography combined with the arsenal of rodent’s brain disease, models can accelerate the neuroscience research and clinical diagnosis of brain disease in the future.


2010 ◽  
Vol 84 (23) ◽  
pp. 12300-12314 ◽  
Author(s):  
Hanna-Mari Tervo ◽  
Oliver T. Keppler

ABSTRACT An immunocompetent, permissive, small-animal model would be valuable for the study of human immunodeficiency virus type 1 (HIV-1) pathogenesis and for the testing of drug and vaccine candidates. However, the development of such a model has been hampered by the inability of primary rodent cells to efficiently support several steps of the HIV-1 replication cycle. Although transgenesis of the HIV receptor complex and human cyclin T1 have been beneficial, additional late-phase blocks prevent robust replication of HIV-1 in rodents and limit the range of in vivo applications. In this study, we explored the HIV-1 susceptibility of rabbit primary T cells and macrophages. Envelope-specific and coreceptor-dependent entry of HIV-1 was achieved by expressing human CD4 and CCR5. A block of HIV-1 DNA synthesis, likely mediated by TRIM5, was overcome by limited changes to the HIV-1 gag gene. Unlike with mice and rats, primary cells from rabbits supported the functions of the regulatory viral proteins Tat and Rev, Gag processing, and the release of HIV-1 particles at levels comparable to those in human cells. While HIV-1 produced by rabbit T cells was highly infectious, a macrophage-specific infectivity defect became manifest by a complex pattern of mutations in the viral genome, only part of which were deamination dependent. These results demonstrate a considerable natural HIV-1 permissivity of the rabbit species and suggest that receptor complex transgenesis combined with modifications in gag and possibly vif of HIV-1 to evade species-specific restriction factors might render lagomorphs fully permissive to infection by this pathogenic human lentivirus.


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