Evaluation of diffusion kurtosis imaging stroke lesion with hemodynamic and metabolic MRI in a rodent model of acute stroke

Objective: Diffusion kurtosis imaging (DKI) has emerged as a new acute stroke imaging approach, augmenting the routine diffusion weighted imaging (DWI). Whereas it has been shown that diffusion lesion without kurtosis abnormality is more likely to recover upon reperfusion while the kurtosis lesion shows poor response, little is known about the underlying pathophysiology between the kurtosis lesion and kurtosis/diffusion lesion mismatch. Materials and methods: We performed multiparametric MRI, including arterial spin labeling (ASL), pH-sensitive amide proton transfer (APT) and DKI in an embolic middle cerebral artery occlusion (MCAO) rodent model of acute stroke. Diffusion and kurtosis lesions were semiautomatically segmented, and multiparametric MRI indices were compared between kurtosis lesion, diffusion lesion, kurtosis/diffusion lesion mismatch and the contralateral normal area. Results: We confirmed a significant difference between diffusion and kurtosis lesion volumes (151 ± 65 vs. 125 ± 47 mm3, P<0.05). Although the ischemic lesions have significantly reduced cerebral blood flow (CBF) from the contralateral normal tissue, we did not find significant CBF difference between kurtosis lesion and the kurtosis/diffusion lesion mismatch (0.53±0.10 vs. 0.47±0.14 ml/g∙min, P>0.05). Importantly, pH in the kurtosis lesion was significantly lower from that of the lesion mismatch (6.81 ± 0.08 vs. 6.89±0.09, P<0.01). Corresponding author: Phillip Zhe Sun, Ph.D. (pzhesun@mgh.harvard.edu), 149-13th Street, Rm-2301, Department of Radiology, MGH and Harvard Medical School, Charlestown, MA 02129 USA, Phone: (617) 726-4060. Fax: (617) 726-7422. ‡These authors contributed equally to this work. IRB Statement: The study has been approved by the local institutional animal care and use committee. Financial Disclosure: No conflict of interest. HHS Public Access Author manuscript AJR Am J Roentgenol. Author manuscript; available in PMC 2019 October 25. Published in final edited form as: AJR Am J Roentgenol. 2018 April ; 210(4): 720–727. doi:10.2214/AJR.17.19134. A uhor M anscript

[1]  Iris Yuwen Zhou,et al.  pH imaging reveals worsened tissue acidification in diffusion kurtosis lesion than the kurtosis/diffusion lesion mismatch in an animal model of acute stroke , 2017, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[2]  Calvin B. Shaw,et al.  Tensor estimation for double‐pulsed diffusional kurtosis imaging , 2017, NMR in biomedicine.

[3]  E. Auriel,et al.  Computed Tomography Perfusion-Based Decision Making for Acute Ischemic Stroke-Missing the Mismatch. , 2017, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[4]  Emiri T. Mandeville,et al.  Fast diffusion kurtosis imaging (DKI) with Inherent COrrelation‐based Normalization (ICON) enhances automatic segmentation of heterogeneous diffusion MRI lesion in acute stroke , 2016, NMR in biomedicine.

[5]  Suk-Tak Chan,et al.  pH-sensitive MRI demarcates graded tissue acidification during acute stroke ― pH specificity enhancement with magnetization transfer and relaxation-normalized amide proton transfer (APT) MRI , 2016, NeuroImage.

[6]  Brian Hansen,et al.  White matter biomarkers from fast protocols using axially symmetric diffusion kurtosis imaging , 2016, NMR in biomedicine.

[7]  Zhiwei Shen,et al.  Parameters of diffusional kurtosis imaging for the diagnosis of acute cerebral infarction in different brain regions , 2016, Experimental and therapeutic medicine.

[8]  Hairong Zheng,et al.  Comparison of image sensitivity between conventional tensor‐based and fast diffusion kurtosis imaging protocols in a rodent model of acute ischemic stroke , 2016, NMR in biomedicine.

[9]  Peter J Basser,et al.  Detecting compartmental non‐Gaussian diffusion with symmetrized double‐PFG MRI , 2015, NMR in biomedicine.

[10]  M. F. Falangola,et al.  Diffusional Kurtosis and Diffusion Tensor Imaging Reveal Different Time-Sensitive Stroke-Induced Microstructural Changes , 2015, Stroke.

[11]  Peter Jezzard,et al.  Identifying the ischaemic penumbra using pH-weighted magnetic resonance imaging , 2014, Brain : a journal of neurology.

[12]  Yu Wang,et al.  Validation of fast diffusion kurtosis MRI for imaging acute ischemia in a rodent model of stroke , 2014, NMR in biomedicine.

[13]  Alexander Leemans,et al.  Can diffusion kurtosis imaging improve the sensitivity and specificity of detecting microstructural alterations in brain tissue chronically after experimental stroke? Comparisons with diffusion tensor imaging and histology , 2014, NeuroImage.

[14]  R. Swartz,et al.  Toward Patient-Tailored Perfusion Thresholds for Prediction of Stroke Outcome , 2014, American Journal of Neuroradiology.

[15]  Brian Hansen,et al.  Experimentally and computationally fast method for estimation of a mean kurtosis , 2013, Magnetic resonance in medicine.

[16]  Catherine Oppenheim,et al.  Diffusion Lesion Reversal After Thrombolysis: A MR Correlate of Early Neurological Improvement , 2012, Stroke.

[17]  J. Helpern,et al.  Stroke Assessment With Diffusional Kurtosis Imaging , 2012, Stroke.

[18]  Ezequiel Farrher,et al.  Diffusion kurtosis imaging and log‐normal distribution function imaging enhance the visualisation of lesions in animal stroke models , 2012, NMR in biomedicine.

[19]  Manabu Inoue,et al.  MRI profile and response to endovascular reperfusion after stroke (DEFUSE 2): a prospective cohort study , 2012, The Lancet Neurology.

[20]  Keiji Ichikawa,et al.  Reversal of Large Ischemic Injury on Hyper-Acute Diffusion MRI , 2012, Case Reports in Neurology.

[21]  Phillip Zhe Sun,et al.  Stratification of Heterogeneous Diffusion MRI Ischemic Lesion With Kurtosis Imaging: Evaluation of Mean Diffusion and Kurtosis MRI Mismatch in an Animal Model of Transient Focal Ischemia , 2012, Stroke.

[22]  Timothy Q. Duong,et al.  Spatiotemporal dynamics of diffusional kurtosis, mean diffusivity and perfusion changes in experimental stroke , 2012, Brain Research.

[23]  Jerry S. Cheung,et al.  Imaging acute ischemic tissue acidosis with pH-sensitive endogenous amide proton transfer (APT) MRI—Correction of tissue relaxation and concomitant RF irradiation effects toward mapping quantitative cerebral tissue pH , 2012, NeuroImage.

[24]  Nadim Joni Shah,et al.  Non-Gaussian diffusion in human brain tissue at high b-factors as examined by a combined diffusion kurtosis and biexponential diffusion tensor analysis , 2011, NeuroImage.

[25]  M. F. Falangola,et al.  Preliminary observations of increased diffusional kurtosis in human brain following recent cerebral infarction , 2011, NMR in biomedicine.

[26]  Phillip Zhe Sun,et al.  Association between pH-Weighted Endogenous Amide Proton Chemical Exchange Saturation Transfer MRI and Tissue Lactic Acidosis during Acute Ischemic Stroke , 2011, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[27]  Thomas Benner,et al.  Fast multislice pH‐weighted chemical exchange saturation transfer (CEST) MRI with Unevenly segmented RF irradiation , 2011, Magnetic resonance in medicine.

[28]  J. Helpern,et al.  MRI quantification of non‐Gaussian water diffusion by kurtosis analysis , 2010, NMR in biomedicine.

[29]  Joshua A Hirsch,et al.  Diffusion weighted imaging reversibility in the brainstem following successful recanalization of acute basilar artery occlusion , 2010, Journal of NeuroInterventional Surgery.

[30]  Kevin C. Chan,et al.  Does diffusion kurtosis imaging lead to better neural tissue characterization? A rodent brain maturation study , 2009, NeuroImage.

[31]  Jinyuan Zhou,et al.  Detection of the Ischemic Penumbra Using pH-Weighted MRI , 2007, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[32]  Jinyuan Zhou,et al.  Simplified quantitative description of amide proton transfer (APT) imaging during acute ischemia , 2007, Magnetic resonance in medicine.

[33]  J. Baron,et al.  How affected is oxygen metabolism in DWI lesions? , 2006, Neurology.

[34]  K. Schmidt,et al.  Comparison of Ischemic Lesion Evolution in Embolic Versus Mechanical Middle Cerebral Artery Occlusion in Sprague Dawley Rats Using Diffusion and Perfusion Imaging , 2006, Stroke.

[35]  Mark W Parsons,et al.  Apparent Diffusion Coefficient Thresholds Do Not Predict the Response to Acute Stroke Thrombolysis , 2005, Stroke.

[36]  David L. Thomas,et al.  Understanding and optimizing the amplitude modulated control for multiple‐slice continuous arterial spin labeling , 2005, Magnetic resonance in medicine.

[37]  J. Alger,et al.  Evolving Paradigms in Neuroimaging of the Ischemic Penumbra , 2004, Stroke.

[38]  Jinyuan Zhou,et al.  Using the amide proton signals of intracellular proteins and peptides to detect pH effects in MRI , 2003, Nature Medicine.

[39]  J. Ranjeva,et al.  Metabolic Counterpart of Decreased Apparent Diffusion Coefficient During Hyperacute Ischemic Stroke: A Brain Proton Magnetic Resonance Spectroscopic Imaging Study , 2003, Stroke.

[40]  M. Chopp,et al.  Postischemic (6-Hour) Treatment With Recombinant Human Tissue Plasminogen Activator and Proteasome Inhibitor PS-519 Reduces Infarction in a Rat Model of Embolic Focal Cerebral Ischemia , 2001, Stroke.

[41]  Gary Duckwiler,et al.  Thrombolytic reversal of acute human cerebral ischemic injury shown by diffusion/perfusion magnetic resonance imaging , 2000, Annals of neurology.

[42]  E. Lo,et al.  Reduction of Tissue Plasminogen Activator-Induced Hemorrhage and Brain Injury by Free Radical Spin Trapping after Embolic Focal Cerebral Ischemia in Rats , 2000, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[43]  G. Schlaug,et al.  The ischemic penumbra: operationally defined by diffusion and perfusion MRI. , 1999, Neurology.

[44]  J. Detre,et al.  Multisection cerebral blood flow MR imaging with continuous arterial spin labeling. , 1998, Radiology.

[45]  J T Vaughan,et al.  Evaluation of 31P metabolite differences in human cerebral gray and white matter , 1998, Magnetic resonance in medicine.

[46]  T. L. Davis,et al.  Hyperacute stroke: evaluation with combined multisection diffusion-weighted and hemodynamically weighted echo-planar MR imaging. , 1996, Radiology.

[47]  P. V. van Zijl,et al.  Diffusion Weighting by the Trace of the Diffusion Tensor within a Single Scan , 1995, Magnetic resonance in medicine.

[48]  Wei Li,et al.  Fast magnetic resonance diffusion‐weighted imaging of acute human stroke , 1992, Neurology.

[49]  B. Rosen,et al.  Perfusion imaging with NMR contrast agents , 1990, Magnetic resonance in medicine.

[50]  J. Kucharczyk,et al.  Early detection of regional cerebral ischemia in cats: Comparison of diffusion‐ and T2‐weighted MRI and spectroscopy , 1990, Magnetic resonance in medicine.