scholarly journals Quantifying MRI T1 relaxation in flowing blood: implications for arterial input function measurement in DCE-MRI

2021 ◽  
Vol 94 (1119) ◽  
pp. 20191004
Author(s):  
Matthew N Gwilliam ◽  
David J Collins ◽  
Martin O Leach ◽  
Matthew R Orton
Keyword(s):  
Contrast Agent ◽  
Flow Velocity ◽  
Pulsatile Flow ◽  
Patient Specific ◽  
High Temporal Resolution ◽  
Dce Mri ◽  
Wide Range ◽  
Non Linear ◽  
Flowing Blood

Objectives: To investigate the feasibility of accurately quantifying the concentration of MRI contrast agent in flowing blood by measuring its T1 in a large vessel. Such measures are often used to obtain patient-specific arterial input functions for the accurate fitting of pharmacokinetic models to dynamic contrast enhanced MRI data. Flow is known to produce errors with this technique, but these have so far been poorly quantified and characterised in the context of pulsatile flow with a rapidly changing T1 as would be expected in vivo. Methods: A phantom was developed which used a mechanical pump to pass fluid at physiologically relevant rates. Measurements of T1 were made using high temporal resolution gradient recalled sequences suitable for DCE-MRI of both constant and pulsatile flow. These measures were used to validate a virtual phantom that was then used to simulate the expected errors in the measurement of an AIF in vivo. Results: The relationship between measured T1 values and flow velocity was found to be non-linear. The subsequent error in quantification of contrast agent concentration in a measured AIF was shown. Conclusions: The T1 measurement of flowing blood using standard DCE- MRI sequences are subject to large measurement errors which are non-linear in relation to flow velocity. Advances in knowledge: This work qualitatively and quantitatively demonstrates the difficulties of accurately measuring the T1 of flowing blood using DCE-MRI over a wide range of physiologically realistic flow velocities and pulsatilities. Sources of error are identified and proposals made to reduce these.

scholarly journals Measuring arterial pulsatility with Dynamic Inflow MAgnitude Contrast (DIMAC)

2021 ◽  
Author(s):  
Joseph R Whittaker ◽  
Fabrizio Fasano ◽  
Marcello Venzi ◽  
Patrick Liebig ◽  
Daniel Gallichan ◽  
...  
Keyword(s):  
Flow Velocity ◽  
Pulsatile Flow ◽  
Cerebral Arteries ◽  
Mr Image ◽  
Signal Contrast ◽  
Within Subjects ◽  
Fast Gradient ◽  
Arterial Tone ◽  
Reliable Methods

Poor arterial health is increasingly recognised as an independent risk factor for cerebrovascular disease, however there remain relatively few reliable methods for assessing the function and health of cerebral arteries. In this study, we outline a new MRI approach to measuring pulsatile flow in cerebral arteries that is based on the inflow phenomenon associated with fast gradient-recalled-echo acquisitions. Unlike traditional phase-contrast techniques, this new method, which we dub Dynamic Inflow MAgnitude Contrast (DIMAC), does not require velocity-encoding gradients as sensitivity to flow velocity results purely from the inflow effect. We achieved this desired effect using a highly accelerated single slice EPI acquisition with very short TR (15 ms) and a 90 degree flip angle, thus maximising inflow contrast. Simulating the spoiled GRE signal in the presence of large arteries and perform a sensitivity analysis to demonstrate that in the regime of high inflow contrast it shows much greater sensitivity to flow velocity over blood volume changes. We support this theoretical prediction with in-vivo data collected in two separate experiments designed to demonstrate the utility of the DIMAC signal contrast. We perform a hypercapnia challenge experiment in order to experimentally modulate arterial tone within subjects, and thus modulate the arterial pulsatile flow waveform. We also perform a thigh-cuff release challenge, designed to induce a transient drop in blood pressure, and demonstrate that the continuous DIMAC signal captures the complex transient change in the pulsatile and non-pulsatile components of flow. In summary, this study proposes a new role for a well established source of MR image contrast, and demonstrate its potential for measuring both steady-state and dynamic changes in arterial tone.

Patient-Specific Simulations in Interventional Cardiology Practice: Early Results From a Clinical/Engineering Centre

2013 ◽  
Author(s):  
Claudio Capelli ◽  
Giorgia M. Bosi ◽  
Daria Cosentino ◽  
Giovanni Biglino ◽  
Sachin Khambadkone ◽  
...  
Keyword(s):  
Fluid Dynamic ◽  
Cardiac Mechanics ◽  
Interventional Cardiology ◽  
Clinical Engineering ◽  
Patient Specific ◽  
Early Results ◽  
Wide Range ◽  
Cfd Analyses ◽  
Engineering Modeling

Patient-specific models have been recently applied to investigate a wide range of cardiovascular problems including cardiac mechanics, hemodynamic conditions and structural interaction with devices [1]. The development of dedicated computational tools which combined the advances in the field of image elaboration, finite element (FE) and computational fluid-dynamic (CFD) analyses has greatly supported not only the understanding of human physiology and pathology, but also the improvement of specific interventions taking into account realistic conditions [2, 3]. However, the translation of these technologies into clinical applications is still a major challenge for the engineering modeling community, which has to compromise between numerical accuracy and response time in order to meet the clinical needs [4]. Hence, the validation of in silico against in vivo results is crucial. Finally, if the development of novel tools has recently attracted big investments [5], it has not been similarly easy to dedicate funds and time to test the developed technologies on large numbers of patient cases.

SU-D-18C-04: The Feasibility of Quantifying MRI Contrast Agent in Pulsatile Flowing Blood Using DCE-MRI

2014 ◽  
Vol 41 (6Part4) ◽  
pp. 121-121
Author(s):  
Gwilliam M N ◽  
Collins D J ◽  
Leach M O ◽  
Orton M R
Keyword(s):  
Contrast Agent ◽  
Mri Contrast Agent ◽  
Mri Contrast ◽  
Dce Mri ◽  
Flowing Blood

Evaluation of 99mTc-Label led Vitamin K4 as an Agent for Testicular Imaging

1991 ◽  
Vol 30 (01) ◽  
pp. 35-39 ◽  
Author(s):  
H. S. Durak ◽  
M. Kitapgi ◽  
B. E. Caner ◽  
R. Senekowitsch ◽  
M. T. Ercan
Keyword(s):  
Soft Tissue ◽  
Room Temperature ◽  
Normal Subjects ◽  
Left Testis ◽  
Wide Range ◽  
Activity Ratios ◽  
The Right ◽  
Radioactivity Levels

Vitamin K4 was labelled with 99mTc with an efficiency higher than 97%. The compound was stable up to 24 h at room temperature, and its biodistribution in NMRI mice indicated its in vivo stability. Blood radioactivity levels were high over a wide range. 10% of the injected activity remained in blood after 24 h. Excretion was mostly via kidneys. Only the liver and kidneys concentrated appreciable amounts of radioactivity. Testis/soft tissue ratios were 1.4 and 1.57 at 6 and 24 h, respectively. Testis/blood ratios were lower than 1. In vitro studies with mouse blood indicated that 33.9 ±9.6% of the radioactivity was associated with RBCs; it was washed out almost completely with saline. Protein binding was 28.7 ±6.3% as determined by TCA precipitation. Blood clearance of 99mTc-l<4 in normal subjects showed a slow decrease of radioactivity, reaching a plateau after 16 h at 20% of the injected activity. In scintigraphic images in men the testes could be well visualized. The right/left testis ratio was 1.08 ±0.13. Testis/soft tissue and testis/blood activity ratios were highest at 3 h. These ratios were higher than those obtained with pertechnetate at 20 min post injection.99mTc-l<4 appears to be a promising radiopharmaceutical for the scintigraphic visualization of testes.

The Filter Loop Technique as a Method of Measuring Platelet Aggregation in the Flowing Blood of the Rat; the Inhibitory Activity of 5-oxo-l-cyclopentene-l-heptanoic Acid (AY-16,804) on Platelet Aggregation

1973 ◽  
Vol 30 (01) ◽  
pp. 138-147 ◽  
Author(s):  
Christopher R. Muirhead
Keyword(s):  
Platelet Aggregation ◽  
Prostaglandin E1 ◽  
Suitable Model ◽  
Heptanoic Acid ◽  
Simple Method ◽  
Loop Technique ◽  
Flowing Blood ◽  
Filter Loop

SummaryThe filter loop technique which measures platelet aggregation in vivo in the flowing-blood of the rat was compared to the optical density technique of Born which is carried out in vitro with platelet rich plasma. Using these two experimental models the effect on platelet aggregation of three known inhibitors sulfinpyrazone, dipyridamole and prostaglandin E1, and a novel compound 5-oxo-l-cyclopentene-l-heptanoic acid (AY-16, 804) was determined.The effects on platelet aggregation of the known inhibitors were consistent with information in the literature. Prostaglandin E1 was the most potent inhibitor in both techniques; sulfinpyrazone inhibited aggregation in both models but was less potent than prostaglandin E1. AY-16, 804 exhibited activity in vitro and in vivo similar to that of sulfinpyrazone. Dipyridamole did not inhibit platelet aggregation in vivo and did not inhibit aggregation in vitro in concentrations at which it remained soluble.The filter loop technique is a suitable model for measuring platelet aggregation in the flowing blood of the rat. It is a relatively simple method of determining aggregation and easily adapted to other species.

Flow velocity and light level drive non-linear response of seagrass Zostera noltei to ammonium enrichment

2016 ◽  
Vol 545 ◽  
pp. 109-121 ◽  
Author(s):  
B Villazán ◽  
FG Brun ◽  
V González‑Ortiz ◽  
F Moreno‑Marín ◽  
TJ Bouma ◽  
...  
Keyword(s):  
Flow Velocity ◽  
Linear Response ◽  
Light Level ◽  
Zostera Noltei ◽  
Non Linear

Ethnomedicinal uses, Phytochemistry and Pharmacological Aspects of the Genus Berberis Linn: A Comprehensive Review

2020 ◽  
Vol 23 ◽  
Author(s):  
Roohi Mohi-ud-din ◽  
Reyaz Hassan Mir ◽  
Prince Ahad Mir ◽  
Saeema Farooq ◽  
Syed Naiem Raza ◽  
...  
Keyword(s):  
Chemical Constituents ◽  
Pharmacological Activities ◽  
Traditional Use ◽  
Comprehensive Review ◽  
Wide Range ◽  
Anti Cancer ◽  
Comprehensive Survey ◽  
Ethnomedicinal Uses

Background: Genus Berberis (family Berberidaceae), which contains about 650 species and 17 genera worldwide, has been used in folklore and various traditional medicine systems. Berberis Linn. is the most established group among genera with around 450-500 species across the world. This comprehensive review will not only help researchers for further evaluation but also provide substantial information for future exploitation of species to develop novel herbal formulations. Objective: The present review is focussed to summarize and collect the updated review of information of Genus Berberis species reported to date regarding their ethnomedicinal information, chemical constituents, traditional/folklore use, and reported pharmacological activities on more than 40 species of Berberis. Conclusion: A comprehensive survey of the literature reveals that various species of the genus possess various phytoconstituents mainly alkaloids, flavonoid based compounds isolated from different parts of a plant with a wide range of pharmacological activities. So far, many pharmacological activities like anti-cancer, anti-hyperlipidemic, hepatoprotective, immunomodulatory, anti-inflammatory both in vitro & in vivo and clinical study of different extracts/isolated compounds of different species of Berberis have been reported, proving their importance as a medicinal plant and claiming their traditional use.

Current Status and Future Perspective for Research on Medicinal Plants with Anticancerous Activity and Minimum Cytotoxic Value

2019 ◽  
Vol 20 (12) ◽  
pp. 1227-1243
Author(s):  
Hina Qamar ◽  
Sumbul Rehman ◽  
D.K. Chauhan
Keyword(s):  
Side Effects ◽  
Medicinal Plants ◽  
Anticancer Agents ◽  
Drug Targets ◽  
Psidium Guajava ◽  
Current Status ◽  
Future Perspective ◽  
Wide Range

Cancer is the second leading cause of morbidity and mortality worldwide. Although chemotherapy and radiotherapy enhance the survival rate of cancerous patients but they have several acute toxic effects. Therefore, there is a need to search for new anticancer agents having better efficacy and lesser side effects. In this regard, herbal treatment is found to be a safe method for treating and preventing cancer. Here, an attempt has been made to screen some less explored medicinal plants like Ammania baccifera, Asclepias curassavica, Azadarichta indica, Butea monosperma, Croton tiglium, Hedera nepalensis, Jatropha curcas, Momordica charantia, Moringa oleifera, Psidium guajava, etc. having potent anticancer activity with minimum cytotoxic value (IC50 >3μM) and lesser or negligible toxicity. They are rich in active phytochemicals with a wide range of drug targets. In this study, these medicinal plants were evaluated for dose-dependent cytotoxicological studies via in vitro MTT assay and in vivo tumor models along with some more plants which are reported to have IC50 value in the range of 0.019-0.528 mg/ml. The findings indicate that these plants inhibit tumor growth by their antiproliferative, pro-apoptotic, anti-metastatic and anti-angiogenic molecular targets. They are widely used because of their easy availability, affordable price and having no or sometimes minimal side effects. This review provides a baseline for the discovery of anticancer drugs from medicinal plants having minimum cytotoxic value with minimal side effects and establishment of their analogues for the welfare of mankind.

Approach in improving potency and selectivity of kinase inhibitors: Allosteric kinase inhibitors

2020 ◽  
Vol 21 ◽  
Author(s):  
Shangfei Wei ◽  
Tianming Zhao ◽  
Jie Wang ◽  
Xin Zhai
Keyword(s):  
Protein Interactions ◽  
Kinase Inhibitors ◽  
Binding Modes ◽  
Allosteric Inhibitors ◽  
Wide Range ◽  
Allosteric Sites ◽  
Protein Functions ◽  
Regulate Protein

: Allostery is an efficient and particular regulatory mechanism to regulate protein functions. Different from conserved orthosteric sites, allosteric sites have distinctive functional mechanism to form the complex regulatory network. In drug discovery, kinase inhibitors targeting the allosteric pockets have received extensive attention for the advantages of high selectivity and low toxicity. The approval of trametinib as the first allosteric inhibitor validated that allosteric inhibitors could be used as effective therapeutic drugs for treatment of diseases. To date, a wide range of allosteric inhibitors have been identified. In this perspective, we outline different binding modes and potential advantages of allosteric inhibitors. In the meantime, the research processes of typical and novel allosteric inhibitors are described briefly in terms of structureactivity relationships, ligand-protein interactions and in vitro and in vivo activity. Additionally, challenges as well as opportunities are presented.

In Silico Assessment of ADME Properties: Advances in Caco-2 Cell Monolayer Permeability Modeling

2019 ◽  
Vol 18 (26) ◽  
pp. 2209-2229 ◽  
Author(s):  
Hai Pham-The ◽  
Miguel Á. Cabrera-Pérez ◽  
Nguyen-Hai Nam ◽  
Juan A. Castillo-Garit ◽  
Bakhtiyor Rasulev ◽  
...  
Keyword(s):  
Intestinal Absorption ◽  
In Silico ◽  
Review Paper ◽  
Cell Monolayer ◽  
Cell Permeability ◽  
Drug Substances ◽  
Wide Range ◽  
Modeling Techniques

One of the main goals of in silico Caco-2 cell permeability models is to identify those drug substances with high intestinal absorption in human (HIA). For more than a decade, several in silico Caco-2 models have been made, applying a wide range of modeling techniques; nevertheless, their capacity for intestinal absorption extrapolation is still doubtful. There are three main problems related to the modest capacity of obtained models, including the existence of inter- and/or intra-laboratory variability of recollected data, the influence of the metabolism mechanism, and the inconsistent in vitro-in vivo correlation (IVIVC) of Caco-2 cell permeability. This review paper intends to sum up the recent advances and limitations of current modeling approaches, and revealed some possible solutions to improve the applicability of in silico Caco-2 permeability models for absorption property profiling, taking into account the above-mentioned issues.

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