Abstract TP348: Quantitative Serial Neuroimaging of Iron in the Intracerebral Hemorrhage Pig Model

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Muhammad E Haque ◽  
Refaat E Gabr ◽  
Xiurong Zhao ◽  
Khader M Hasan ◽  
Ponnada A Narayana ◽  
...  

Objective: To serially quantify changes of iron concentration within hematomas in the intracerebral hemorrhage (ICH) pig model using non-invasive R2* and quantitative susceptibility mapping (QSM) MRI methods. Introduction: Hemolysis-related release of hemoglobin/heme/free iron after ICH causes cytotoxic injury. An accurate post hemorrhage assessment of iron would be valuable to develop strategies to prevent secondary damage. The T2* relaxation rate (R2* =1/T2*) on MRI depends on the regional oxy- versus deoxyhemoglobin. Post-ICH excess of deoxyhemoglobin has been applied as a quantitative marker to estimate iron in the brain. However, quantitative susceptibility mapping (QSM) is a new MRI technique that can quantify iron concentration within the hematoma by measuring induced magnetic susceptibility. Using R2* mapping and QSM in a large animal ICH model, we measured spatiotemporal changes in iron concentration in the brain. Methods: Lobar ICH was induced by infusion of 2.5 ml autologous blood in 8 Yorkshire pigs with average age/wt of 4-6wk/12.5±2.5kg. MRI was obtained at days 1 and 7. A 3D anatomical and multi-echo gradient echo images were obtained on a clinical 3.0 T Philips Ingenia MRI system. Parametric R2* and susceptibility maps were generated. Regions of interest were placed within hematoma and contralesional CSF. Results: R2* measurements in the hematoma at day 1 and day 7 were 41.3 ± 7.3 and 37.7 ± 7.7 s -1 , respectively, whereas the corresponding susceptibility measurements were 0.75± 0.3 and 0.70 ± 0.5 ppm. The CSF R2* were 5.53 ± 2.1 and 6.85 ± 2.4 s -1 , whereas susceptibility showed 0.06 ± 0.16 and 0.02 ± 0.03 ppm at the two time points. Both R2* and QSM showed no significant change in iron concentration within the hematoma ROI with p-value of 0.18 and 0.72 over a week. Absence of hyperintense regions remote from the hematoma in susceptibility maps suggested lack of diffuse iron deposition. Good correlation was observed between R2* and QSM (correlation coefficient 0.83 and 0.78 within hematoma, and -0.66 and -0.07 within CSF, at day 1 and 7, respectively). Conclusion: R2* and especially QSM, with their ability to provide quantitative iron content, are valuable tools to test new ICH treatments particularly targeting iron in this large animal model.

2018 ◽  
Vol 38 (3) ◽  
pp. 375-381 ◽  
Author(s):  
Muhammad E Haque ◽  
Refaat E Gabr ◽  
Xiurong Zhao ◽  
Khader M Hasan ◽  
Andrew Valenzuela ◽  
...  

Iron released after intracerebral hemorrhage (ICH) is damaging to the brain. Measurement of the content and distribution of iron in the hematoma could predict brain damage. In this study, 16 Yorkshire piglets were subjected to autologous blood injection ICH model and studied longitudinally using quantitative susceptibility mapping and R2* relaxivity MRI on day 1 and 7 post-ICH. Phantom calibration of susceptibility demonstrated (1) iron distribution heterogeneity within the hematoma and (2) natural absorption of iron from 154 ± 78 µg/mL (day 1) to 127 ± 33 µg/mL (day 7). R2* in the hematoma decreased at day 7. This method could be adopted for ICH in humans.


2019 ◽  
Vol 51 (3) ◽  
pp. 712-718 ◽  
Author(s):  
Ashmita De ◽  
Hongfu Sun ◽  
Derek J. Emery ◽  
Kenneth S. Butcher ◽  
Alan H. Wilman

NeuroImage ◽  
2013 ◽  
Vol 78 ◽  
pp. 68-74 ◽  
Author(s):  
Weili Zheng ◽  
Helen Nichol ◽  
Saifeng Liu ◽  
Yu-Chung N. Cheng ◽  
E. Mark Haacke

NeuroImage ◽  
2012 ◽  
Vol 59 (3) ◽  
pp. 2625-2635 ◽  
Author(s):  
Berkin Bilgic ◽  
Adolf Pfefferbaum ◽  
Torsten Rohlfing ◽  
Edith V. Sullivan ◽  
Elfar Adalsteinsson

2018 ◽  
Author(s):  
Phillip G. D. Ward ◽  
Ian H Harding ◽  
Thomas G. Close ◽  
Louise A Corben ◽  
Martin B Delatycki ◽  
...  

AbstractBackgroundFriedreich ataxia is a recessively inherited, progressive neurological disease characterised by impaired mitochondrial iron metabolism. The dentate nuclei of the cerebellum are characteristic sites of neurodegeneration in the disease, but little is known of the longitudinal progression of pathology in these structures.MethodsUsing in vivo magnetic resonance imaging, including quantitative susceptibility mapping, we investigated changes in iron concentration and volume in the dentate nuclei in individuals with Friedreich ataxia (n=20) and healthy controls (n=18) over a two-year period.ResultsThe longitudinal rate of iron concentration was significantly elevated bilaterally in participants with Friedreich ataxia relative to healthy controls. Atrophy rates did not differ significantly between groups. Change in iron concentration and atrophy both correlated with baseline disease severity or duration, indicating sensitivity of these measures to disease stage. Moreover, atrophy was maximal in individuals early in the disease course, while the rate of iron concentration increased with disease progression.ConclusionsProgressive dentate nuclei pathology is evident in vivo in Friedreich ataxia, and the rates of change of iron concentration and atrophy in these structures are sensitive to the disease stage. The findings are consistent with an increased rate of iron concentration and atrophy early in the disease, followed by iron accumulation and stable volume in later stages. This pattern suggests that iron dysregulation persists after loss of the vulnerable neurons in the dentate. The significant changes observed over a two-year period highlights the utility of quantitative susceptibility mapping as a longitudinal biomarker and staging tool.


2020 ◽  
Author(s):  
Anton Abyzov ◽  
Bernard E. Van Beers ◽  
Philippe Garteiser

Abdominal quantitative susceptibility mapping (QSM), especially in small animals, is challenging because of respiratory motion and blood flow that, in addition to noise, deteriorate the quality of the input data. Efficient artefact suppression in QSM reconstruction is crucial in these conditions. Single-step QSM algorithms combine background field removal and magnetic field-to-susceptibility inverse problem regularization in a single optimization equation. Here, we propose a single-step QSM algorithm that uses spherical mean value kernels of different radii for background field removal and structure prior (consistency with magnitude image) with L1 norm for regularization. The optimization problem is solved using the split-Bregman method on the graphic processor unit. The method was compared with previously reported singlestep methods: a method using discrete Laplacian instead of spherical mean value kernels, a method using total variational penalty instead of structure prior, and a method using L2 norm for structure prior. With the proposed method relative to the previous ones, a numerical susceptibility phantom was reconstructed more precisely. In living mice, susceptibility maps with more homogeneous liver, higher contrast between liver and blood vessels, and well-preserved structural details were obtained. In patients, susceptibility maps with more homogeneous subcutaneous fat and higher contrast between subcutaneous fat and liver were obtained. These results show the potential of the proposed single-step method for abdominal QSM in small animals and humans.


2018 ◽  
Vol 39 (12) ◽  
pp. 2521-2535 ◽  
Author(s):  
Johannes Boltze ◽  
Fabienne Ferrara ◽  
Atticus H Hainsworth ◽  
Leslie R Bridges ◽  
Marietta Zille ◽  
...  

Intracerebral hemorrhage (ICH) is an important stroke subtype, but preclinical research is limited by a lack of translational animal models. Large animal models are useful to comparatively investigate key pathophysiological parameters in human ICH. To (i) establish an acute model of moderate ICH in adult sheep and (ii) an advanced neuroimage processing pipeline for automatic brain tissue and hemorrhagic lesion determination; 14 adult sheep were assigned for stereotactically induced ICH into cerebral white matter under physiological monitoring. Six hours after ICH neuroimaging using 1.5T MRI including structural as well as perfusion and diffusion, weighted imaging was performed before scarification and subsequent neuropathological investigation including immunohistological staining. Controlled, stereotactic application of autologous blood caused a space-occupying intracerebral hematoma of moderate severity, predominantly affecting white matter at 5 h post-injection. Neuroimage post-processing including lesion probability maps enabled automatic quantification of structural alterations including perilesional diffusion and perfusion restrictions. Neuropathological and immunohistological investigation confirmed perilesional vacuolation, axonal damage, and perivascular blood as seen after human ICH. The model and imaging platform reflects key aspects of human ICH and enables future translational research on hematoma expansion/evacuation, white matter changes, hematoma evacuation, and other aspects.


2019 ◽  
Vol 13 (2) ◽  
pp. 90-113
Author(s):  
Feng Lin ◽  
Martin R. Prince ◽  
Pascal Spincemaille ◽  
Yi Wang

<P>Background: Quantitative susceptibility mapping (QSM) depicts biodistributions of tissue magnetic susceptibility sources, including endogenous iron and calcifications, as well as exogenous paramagnetic contrast agents and probes. When comparing QSM with simple susceptibility weighted MRI, QSM eliminates blooming artifacts and shows reproducible tissue susceptibility maps independent of field strength and scanner manufacturer over a broad range of image acquisition parameters. For patient care, QSM promises to inform diagnosis, guide surgery, gauge medication, and monitor drug delivery. The Bayesian framework using MRI phase data and structural prior knowledge has made QSM sufficiently robust and accurate for routine clinical practice.Objective:To address the lack of a summary of US patents that is valuable for QSM product development and dissemination into the MRI community.Method:We searched the USPTO Full-Text and Image Database for patents relevant to QSM technology innovation. We analyzed the claims of each patent to characterize the main invented method and we investigated data on clinical utility. </P><P> Results: We identified 17 QSM patents; 13 were implemented clinically, covering various aspects of QSM technology, including the Bayesian framework, background field removal, numerical optimization solver, zero filling, and zero-TE phase.Conclusion:Our patent search identified patents that enable QSM technology for imaging the brain and other tissues. QSM can be applied to study a wide range of diseases including neurological diseases, liver iron disorders, tissue ischemia, and osteoporosis. MRI manufacturers can develop QSM products for more seamless integration into existing MRI scanners to improve medical care.</P>


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