Early Experience of Translating pH-Weighted MRI to Image Human Subjects at 3 Tesla

Background and Purpose— In acute stroke, mismatch between lesions seen on diffusion- (DWI) and perfusion-weighted (PWI) MRI has been used to identify ischemic tissue before irreversible damage. Nevertheless, the concept of PWI/DWI mismatch is oversimplified and the ischemic tissue metabolic status and outcome are often heterogeneous. Tissue pH, a well-regulated physiological index that alters on disrupted tissue metabolism, may provide a surrogate metabolic imaging marker that augments the DWI and PWI for penumbra imaging. Methods— pH-weighted MRI was obtained by probing the pH-dependent amide proton transfer between endogenous mobile proteins/peptides and tissue water. The technique was validated using animal stroke models, optimized for human use, and preliminarily tested for imaging healthy volunteers. Results— pH-weighted MRI is sensitive and specific to ischemic tissue acidosis. pH MRI can be optimized for clinical use, and a pilot human study showed it is feasible using a standard 3 Tesla MRI scanner. Conclusions— Ischemic acidosis can be imaged via an endogenous pH-weighted MRI technique, which complements conventional PWI and DWI for penumbra imaging. pH-weighted MRI has been optimized and appears feasible and practical in imaging human subjects. Additional study is necessary to elucidate the diagnostic use of pH MRI in stroke patients.

[1]  S. Warach,et al.  Evidence of Reperfusion Injury, Exacerbated by Thrombolytic Therapy, in Human Focal Brain Ischemia Using a Novel Imaging Marker of Early Blood–Brain Barrier Disruption , 2004, Stroke.

[2]  A. Furlan,et al.  Use of tissue-type plasminogen activator for acute ischemic stroke: the Cleveland area experience. , 2000, JAMA.

[3]  R. Gonzalez,et al.  Imaging-guided acute ischemic stroke therapy: From "time is brain" to "physiology is brain". , 2006, AJNR. American journal of neuroradiology.

[4]  Patrick McElduff,et al.  Pretreatment Diffusion- and Perfusion-MR Lesion Volumes Have a Crucial Influence on Clinical Response to Stroke Thrombolysis , 2010, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[5]  M. Welsh,et al.  Neuroprotection in Ischemia Blocking Calcium-Permeable Acid-Sensing Ion Channels , 2004, Cell.

[6]  R S Balaban,et al.  Determination of pH using water protons and chemical exchange dependent saturation transfer (CEST) , 2000, Magnetic resonance in medicine.

[7]  A Gregory Sorensen,et al.  Assessing tissue viability with MR diffusion and perfusion imaging. , 2003, AJNR. American journal of neuroradiology.

[8]  C. Weiller,et al.  Predictors of Apparent Diffusion Coefficient Normalization in Stroke Patients , 2004, Stroke.

[9]  Thomas Benner,et al.  Investigation of optimizing and translating pH‐sensitive pulsed‐chemical exchange saturation transfer (CEST) imaging to a 3T clinical scanner , 2008, Magnetic resonance in medicine.

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

[11]  R. O’Connor,et al.  Thrombolytic therapy for acute ischemic stroke: why the majority of patients remain ineligible for treatment. , 1999, Annals of emergency medicine.

[12]  Risto A Kauppinen,et al.  Proton transfer ratio, lactate, and intracellular pH in acute cerebral ischemia , 2007, Magnetic resonance in medicine.

[13]  Koroshetz Wj,et al.  Tissue plasminogen activator for acute ischemic stroke. , 1996, The New England journal of medicine.

[14]  R. Luepker,et al.  Delayed Hospital Arrival for Acute Stroke: The Minnesota Stroke Survey , 1998, Annals of Internal Medicine.

[15]  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.

[16]  W. Heiss,et al.  Does the Mismatch Match the Penumbra?: Magnetic Resonance Imaging and Positron Emission Tomography in Early Ischemic Stroke , 2005, Stroke.

[17]  J. Alger,et al.  Beyond Mismatch: Evolving Paradigms in Imaging the Ischemic Penumbra With Multimodal Magnetic Resonance Imaging , 2003, Stroke.

[18]  S. Warach,et al.  Magnetic Resonance Imaging Criteria for Thrombolysis in Acute Cerebral Infarct , 2005, Stroke.

[19]  A Gregory Sorensen,et al.  Correction for artifacts induced by B0 and B1 field inhomogeneities in pH‐sensitive chemical exchange saturation transfer (CEST) imaging , 2007, Magnetic resonance in medicine.

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

[21]  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.

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

[23]  A. Demchuk,et al.  Why are stroke patients excluded from TPA therapy? , 2001, Neurology.

[24]  S M Davis,et al.  Pathophysiological topography of acute ischemia by combined diffusion-weighted and perfusion MRI. , 1999, Stroke.

[25]  A Gregory Sorensen,et al.  Imaging pH using the chemical exchange saturation transfer (CEST) MRI: Correction of concomitant RF irradiation effects to quantify CEST MRI for chemical exchange rate and pH , 2008, Magnetic resonance in medicine.

[26]  B. Siesjö.  Pathophysiology and treatment of focal cerebral ischemia. Part II: Mechanisms of damage and treatment. , 1992, Journal of neurosurgery.

[27]  B. Siesjö,et al.  Thresholds in cerebral ischemia - the ischemic penumbra. , 1981, Stroke.

[28]  K. Hossmann.  Viability thresholds and the penumbra of focal ischemia , 1994, Annals of neurology.

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

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

[31]  L. Østergaard,et al.  Characterizing physiological heterogeneity of infarction risk in acute human ischaemic stroke using MRI. , 2006, Brain : a journal of neurology.

[32]  Joseph P. Broderick,et al.  Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. , 1995 .

[33]  S. Warach.  Thrombolysis in stroke beyond three hours: Targeting patients with diffusion and perfusion MRI , 2002, Annals of neurology.

[34]  Michael Brady,et al.  Improved Optimization for the Robust and Accurate Linear Registration and Motion Correction of Brain Images , 2002, NeuroImage.

[35]  K A Hossmann,et al.  Imaging of brain tissue pH and metabolites. A new approach for the validation of volume‐selective NMR spectroscopy , 1989, NMR in biomedicine.

[36]  H. Ellis.  stroke , 1997, The Lancet.

[37]  S. Warach,et al.  MRI Screening Before Standard Tissue Plasminogen Activator Therapy Is Feasible and Safe , 2005, Stroke.

[38]  Mark W. Woolrich,et al.  Bayesian analysis of neuroimaging data in FSL , 2009, NeuroImage.

[39]  G. Donnan,et al.  Selection of thrombolytic therapy beyond 3 h using magnetic resonance imaging , 2005, Current opinion in neurology.