Multiparametric classification of sub‐acute ischemic stroke recovery with ultrafast diffusion, 23Na, and MPIO‐labeled stem cell MRI at 21.1 T

MRI leverages multiple modes of contrast to characterize stroke. High‐magnetic‐field systems enhance the performance of these MRI measurements. Previously, we have demonstrated that individually sodium and stem cell tracking metrics are enhanced at ultrahigh field in a rat model of stroke, and we have developed robust single‐scan diffusion‐weighted imaging approaches that utilize spatiotemporal encoding (SPEN) of the apparent diffusion coefficient (ADC) for these challenging field strengths. Here, we performed a multiparametric study of middle cerebral artery occlusion (MCAO) biomarker evolution focusing on comparison of these MRI biomarkers for stroke assessment during sub‐acute recovery in rat MCAO models at 21.1 T. T2‐weighted MRI was used as the benchmark for identification of the ischemic lesion over the course of the study. The number of MPIO‐induced voids measured by gradient‐recalled echo, the SPEN measurement of ADC, and 23Na MRI values were determined in the ischemic area and contralateral hemisphere, and relative performances for stroke classification were compared by receiver operator characteristic analysis. These measurements were associated with unique time‐dependent trajectories during stroke recovery that changed the sensitivity and specificity for stroke monitoring during its evolution. Advantages and limitations of these contrasts, and the use of ultrahigh field for multiparametric stroke assessment, are discussed.

[1]  Alan P. Koretsky,et al.  In vivo labeling of adult neural progenitors for MRI with micron sized particles of iron oxide: Quantification of labeled cell phenotype , 2009, NeuroImage.

[2]  G. Stanisz,et al.  Effectiveness of micron‐sized superparamagnetic iron oxide particles as markers for detection of migration of bone marrow‐derived mesenchymal stromal cells in a stroke model , 2013, Journal of magnetic resonance imaging : JMRI.

[3]  T. Duong,et al.  Dynamic Tracking of Acute Ischemic Tissue Fates Using Improved Unsupervised ISODATA Analysis of High-Resolution Quantitative Perfusion and Diffusion Data , 2004, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[4]  R. Bammer,et al.  The Infarct Core is Well Represented by the Acute Diffusion Lesion: Sustained Reversal is Infrequent , 2012, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[5]  Marc Fisher,et al.  Long-Term Changes of Functional MRI–Based Brain Function, Behavioral Status, and Histopathology After Transient Focal Cerebral Ischemia in Rats , 2006, Stroke.

[6]  J D Fenstermacher,et al.  Transient and permanent resolution of ischemic lesions on diffusion-weighted imaging after brief periods of focal ischemia in rats : correlation with histopathology. , 2000, Stroke.

[7]  Timothy Q Duong,et al.  Quantitative prediction of ischemic stroke tissue fate , 2008, NMR in biomedicine.

[8]  T. Duong,et al.  Intraarterial transplantation of human umbilical cord blood mononuclear cells in hyperacute stroke improves vascular function , 2017, Stem Cell Research & Therapy.

[9]  Lothar R. Schad,et al.  30 years of sodium/X-nuclei magnetic resonance imaging , 2014, Magnetic Resonance Materials in Physics, Biology and Medicine.

[10]  M. Davidson,et al.  Intracellular SPIO labeling of microglia: high field considerations and limitations for MR microscopy. , 2012, Contrast media & molecular imaging.

[11]  S. Grant,et al.  Transverse relaxation of selectively excited metabolites in stroke at 21.1 T , 2017, Magnetic resonance in medicine.

[12]  M. Davidson,et al.  Magnetic resonance contrast and biological effects of intracellular superparamagnetic iron oxides on human mesenchymal stem cells with long-term culture and hypoxic exposure. , 2013, Cytotherapy.

[13]  Timothy Q. Duong,et al.  Pixel-by-Pixel Spatiotemporal Progression of Focal Ischemia Derived Using Quantitative Perfusion and Diffusion Imaging , 2003, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[14]  M. Wintermark,et al.  Advanced Neuroimaging of Acute Ischemic Stroke: Penumbra and Collateral Assessment. , 2018, Neuroimaging clinics of North America.

[15]  Timothy P L Roberts,et al.  Diffusion weighted magnetic resonance imaging in stroke. , 2003, European journal of radiology.

[16]  S. Grant,et al.  Intracellular labeling of mouse embryonic stem cell-derived neural progenitor aggregates with micron-sized particles of iron oxide. , 2015, Cytotherapy.

[17]  J. R. Long,et al.  Ultra-wide bore 900 MHz high-resolution NMR at the National High Magnetic Field Laboratory. , 2005, Journal of magnetic resonance.

[18]  J. Miller,et al.  Transient Focal Cerebral Ischemia , 2001 .

[19]  M. Wintermark,et al.  Multiparametric Magnetic Resonance Imaging for Prediction of Parenchymal Hemorrhage in Acute Ischemic Stroke After Reperfusion Therapy , 2017, Stroke.

[20]  Reiner Umathum,et al.  39K and 23Na relaxation times and MRI of rat head at 21.1 T , 2016, NMR in biomedicine.

[21]  S. Grant,et al.  Tracking mesenchymal stem cells using magnetic resonance imaging , 2016, Brain circulation.

[22]  X. Golay,et al.  Sodium (23Na) ultra-short echo time imaging in the human brain using a 3D-Cones trajectory , 2013, Magnetic Resonance Materials in Physics, Biology and Medicine.

[23]  W. Heiss,et al.  Multiparametric Model for Penumbral Flow Prediction in Acute Stroke , 2017, Stroke.

[24]  S. Grant,et al.  A Decade of Experience With the UltraWide-Bore 900-MHz NMR Magnet , 2015, IEEE Transactions on Applied Superconductivity.

[25]  P. Barber,et al.  Early T1- and T2-weighted MRI signatures of transient and permanent middle cerebral artery occlusion in a murine stroke model studied at 9.4T , 2005, Neuroscience Letters.

[26]  Lucio Frydman,et al.  Reducing SAR requirements in multislice volumetric single‐shot spatiotemporal MRI by two‐dimensional RF pulses , 2017, Magnetic resonance in medicine.

[27]  L. Schad,et al.  Investigating potentially salvageable penumbra tissue in an in vivo model of transient ischemic stroke using sodium, diffusion, and perfusion magnetic resonance imaging , 2016, BMC Neuroscience.

[28]  Lucio Frydman,et al.  Ultrafast in vivo diffusion imaging of stroke at 21.1 T by spatiotemporal encoding , 2015, Magnetic resonance in medicine.

[29]  Nils Daniel Forkert,et al.  Classifiers for Ischemic Stroke Lesion Segmentation: A Comparison Study , 2015, PloS one.

[30]  J. Kucharczyk,et al.  Diffusion/perfusion MR imaging of acute cerebral ischemia , 1991, Magnetic resonance in medicine.

[31]  Lucio Frydman,et al.  Toward 20 T magnetic resonance for human brain studies: opportunities for discovery and neuroscience rationale , 2016, Magnetic Resonance Materials in Physics, Biology and Medicine.

[32]  Hsiao-Ying Wey,et al.  A review of current imaging methods used in stroke research , 2013, Neurological research.

[33]  Raphael Guzman,et al.  Cell Transplantation Therapy for Stroke , 2007, Stroke.

[34]  D. Kraitchman,et al.  Imaging of stem cells using MRI , 2008, Basic Research in Cardiology.

[35]  Max Wintermark,et al.  Multiparametric MRI and CT Models of Infarct Core and Favorable Penumbral Imaging Patterns in Acute Ischemic Stroke , 2013, Stroke.

[36]  E F Halpern,et al.  Frequency and clinical context of decreased apparent diffusion coefficient reversal in the human brain. , 2001, Radiology.

[37]  Michal Irani,et al.  Super‐resolved spatially encoded single‐scan 2D MRI , 2010, Magnetic resonance in medicine.

[38]  S. Grant,et al.  Initial in vivo rodent sodium and proton MR imaging at 21.1 T. , 2010, Magnetic resonance imaging.

[39]  M. Wintermark,et al.  Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association , 2013, Stroke.

[40]  Scott Hamilton,et al.  Magnetic resonance imaging profiles predict clinical response to early reperfusion: The diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study , 2006, Annals of neurology.

[41]  N. Bornstein,et al.  Classification of lesion area in stroke patients during the subacute phase: A multiparametric MRI study , 2014, Magnetic resonance in medicine.

[42]  K R Thulborn,et al.  Comprehensive MR imaging protocol for stroke management: tissue sodium concentration as a measure of tissue viability in nonhuman primate studies and in clinical studies. , 1999, Radiology.

[43]  Christian Beaulieu,et al.  Relationship between sodium intensity and perfusion deficits in acute ischemic stroke , 2011, Journal of magnetic resonance imaging : JMRI.

[44]  Lucio Frydman,et al.  New spatiotemporal approaches for fully refocused, multislice ultrafast 2D MRI , 2014, Magnetic resonance in medicine.

[45]  W. Powers,et al.  2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association , 2018, Stroke.

[46]  R. Guzman,et al.  Intra-Arterial Injection of Neural Stem Cells using a Microneedle Technique does not Cause Microembolic Strokes , 2011, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[47]  W. Powers,et al.  Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. , 2019, Stroke.

[48]  Lucio Frydman,et al.  Diffusion weighted MRI by spatiotemporal encoding: analytical description and in vivo validations. , 2013, Journal of magnetic resonance.

[49]  A. Fagan,et al.  Sodium-23 Magnetic Resonance Imaging Has Potential for Improving Penumbra Detection but Not for Estimating Stroke Onset Time , 2015, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[50]  Ling Wei,et al.  Transplantation of hypoxia preconditioned bone marrow mesenchymal stem cells enhances angiogenesis and neurogenesis after cerebral ischemia in rats , 2012, Neurobiology of Disease.

[51]  F. Wetterling,et al.  Sodium-23 magnetic resonance imaging during and after transient cerebral ischemia: multinuclear stroke protocols for double-tuned 23Na/1H resonator systems , 2012, Physics in medicine and biology.