Visualizing non-Gaussian diffusion: clinical application of q-space imaging and diffusional kurtosis imaging of the brain and spine.

Recently, non-Gaussian diffusion-weighted imaging (DWI) techniques, including q-space imaging (QSI) and diffusional kurtosis imaging (DKI), have emerged as advanced methods to evaluate tissue microstructure in vivo using water diffusion. QSI and DKI have shown promising results in clinical applications, such as in the evaluation of brain tumors (e.g., grading gliomas), degenerative diseases (e.g., specific diagnosis of Parkinson disease), demyelinating diseases (e.g., assessment of normal-appearing tissue of multiple sclerosis), and cerebrovascular diseases (e.g., assessment of the microstructural environment of fresh infarctions). Representative metrics in clinical use are the full width at half maximum, also known as the mean displacement of the probability density function curve, which is derived from QSI, and diffusional kurtosis, which is derived from DKI. These new metrics may provide information on tissue structure in addition to that provided by conventional Gaussian DWI investigations that use the apparent diffusion coefficient and fractional anisotropy, recognized indices for evaluating disease and normal development in the brain and spine. In some clinical situations, sensitivity for detecting pathological conditions is higher using QSI and DKI than conventional DWI and diffusion tensor imaging (DTI) because DWI and DTI calculations are based on the assumption that water molecules follow a Gaussian distribution, whereas hindrance of the distribution of water molecules by complex and restricted structures in actual neural tissues produces distributions that are far from Gaussian. We review the technical aspects and clinical applications of QSI and DKI, focusing on clinical use and in vivo studies and highlighting differences from conventional diffusional metrics.

[1]  Y. Cohen,et al.  Structural information in neuronal tissue as revealed by q‐space diffusion NMR spectroscopy of metabolites in bovine optic nerve , 1999, NMR in biomedicine.

[2]  M E Moseley,et al.  Evaluation of early reperfusion and IV tPA therapy using diffusion- and perfusion-weighted MRI , 1999, Neurology.

[3]  Mathias Hoehn,et al.  Diffusion-Weighted Imaging in Acute Stroke – A Tool of Uncertain Value? , 2002, Cerebrovascular Diseases.

[4]  M. Chopp,et al.  MRI evaluation of white matter recovery after brain injury. , 2010, Stroke.

[5]  James M Provenzale,et al.  Lymphomas and high-grade astrocytomas: comparison of water diffusibility and histologic characteristics. , 2002, Radiology.

[6]  K. Kiuchi,et al.  Fractional Anisotropy–Threshold Dependence in Tract-Based Diffusion Tensor Analysis: Evaluation of the Uncinate Fasciculus in Alzheimer Disease , 2009, American Journal of Neuroradiology.

[7]  M. Harada,et al.  Change of diffusion anisotropy in patients with acute cerebral infarction using statistical parametric analysis , 2006, Radiation Medicine.

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

[9]  Masaaki Hori,et al.  Mean displacement map of spine and spinal cord disorders using high b-value q-space imaging-feasibility study , 2011, Acta radiologica.

[10]  Adriana Di Martino,et al.  Preliminary evidence of altered gray and white matter microstructural development in the frontal lobe of adolescents with attention‐deficit hyperactivity disorder: A diffusional kurtosis imaging study , 2011, Journal of magnetic resonance imaging : JMRI.

[11]  Jonathan Z. Simon,et al.  Diffusion kurtosis as an in vivo imaging marker for reactive astrogliosis in traumatic brain injury , 2012, NeuroImage.

[12]  Toshiaki Taoka,et al.  Uncinate fasciculus‐correlated cognition in Alzheimer's disease: a diffusion tensor imaging study by tractography , 2010, Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society.

[13]  Kaoru Kurisu,et al.  Apparent diffusion coefficient of human brain tumors at MR imaging. , 2005, Radiology.

[14]  Marco Rovaris,et al.  Occult tissue damage in patients with primary progressive multiple sclerosis is independent of T2-visible lesions , 2003, Journal of Neurology.

[15]  M. Behen,et al.  Alterations in frontal lobe tracts and corpus callosum in young children with autism spectrum disorder. , 2010, Cerebral cortex.

[16]  C. Hardy,et al.  Accelerated diffusion spectrum imaging in the human brain using compressed sensing , 2011, Magnetic resonance in medicine.

[17]  T. Hendler,et al.  High b‐value q‐space analyzed diffusion‐weighted MRI: Application to multiple sclerosis , 2002, Magnetic resonance in medicine.

[18]  Osamu Abe,et al.  Diffusion tensor tract-specific analysis of the uncinate fasciculus in patients with amyotrophic lateral sclerosis , 2010, Neuroradiology.

[19]  F. Liu,et al.  In the assessment of supratentorial glioma grade: the combined role of multivoxel proton MR spectroscopy and diffusion tensor imaging. , 2011, Clinical radiology.

[20]  Toshinori Hirai,et al.  Grading astrocytic tumors by using apparent diffusion coefficient parameters: superiority of a one- versus two-parameter pilot method. , 2009, Radiology.

[21]  S. Ng,et al.  Primary Cerebral Lymphoma and Glioblastoma Multiforme: Differences in Diffusion Characteristics Evaluated with Diffusion Tensor Imaging , 2008, American Journal of Neuroradiology.

[22]  K. Kono,et al.  The role of diffusion-weighted imaging in patients with brain tumors. , 2001, AJNR. American journal of neuroradiology.

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

[24]  G J Barker,et al.  Investigation of MS normal-appearing brain using diffusion tensor MRI with clinical correlations , 2001, Neurology.

[25]  S. Aoki,et al.  New diffusion metrics for spondylotic myelopathy at an early clinical stage , 2012, European Radiology.

[26]  Jan Sijbers,et al.  Gliomas: diffusion kurtosis MR imaging in grading. , 2012, Radiology.

[27]  O. Abe,et al.  [Magnetic resonance diffusion tractography in the brain--its application and limitation]. , 2007, Brain and nerve = Shinkei kenkyu no shinpo.

[28]  Markus Nilsson,et al.  In vivo visualization of displacement-distribution-derived parameters in q-space imaging. , 2008, Magnetic resonance imaging.

[29]  K. Hikishima,et al.  Volumetric q-space imaging by 3D diffusion-weighted MRI. , 2008, Magnetic resonance imaging.

[30]  B. Ardekani,et al.  Estimation of tensors and tensor‐derived measures in diffusional kurtosis imaging , 2011, Magnetic resonance in medicine.

[31]  Osamu Abe,et al.  The optimal trackability threshold of fractional anisotropy for diffusion tensor tractography of the corticospinal tract. , 2004, Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine.

[32]  Yi-Hsin Weng,et al.  Parkinson disease: diagnostic utility of diffusion kurtosis imaging. , 2011, Radiology.

[33]  Yaniv Assaf,et al.  Hypertension and neuronal degeneration in excised rat spinal cord studied by high-b value q-space diffusion magnetic resonance imaging , 2003, Experimental Neurology.

[34]  Talma Hendler,et al.  White matter changes in multiple sclerosis: correlation of q-space diffusion MRI and 1H MRS. , 2005, Magnetic resonance imaging.

[35]  Marco Rovaris,et al.  Short-term accrual of gray matter pathology in patients with progressive multiple sclerosis: an in vivo study using diffusion tensor MRI , 2005, NeuroImage.

[36]  Peter C M van Zijl,et al.  High b‐value q‐space diffusion‐weighted MRI of the human cervical spinal cord in vivo: Feasibility and application to multiple sclerosis , 2008, Magnetic resonance in medicine.

[37]  Usha Sinha,et al.  Relationships Between Choline Magnetic Resonance Spectroscopy, Apparent Diffusion Coefficient and Quantitative Histopathology in Human Glioma , 2000, Journal of Neuro-Oncology.

[38]  Y. Cohen,et al.  High b‐value q‐space analyzed diffusion‐weighted MRS and MRI in neuronal tissues – a technical review , 2002, NMR in biomedicine.

[39]  S. Maier,et al.  Apparent diffusion coefficient and fractional anisotropy in spinal cord: Age and cervical spondylosis–related changes , 2005, Journal of magnetic resonance imaging : JMRI.

[40]  R. Zimmerman,et al.  Is there a role for diffusion-weighted imaging in patients with brain tumors or is the "bloom off the rose"? , 2001, AJNR. American journal of neuroradiology.

[41]  P. Basser,et al.  MR diffusion tensor spectroscopy and imaging. , 1994, Biophysical journal.

[42]  Adriana Di Martino,et al.  Age‐related non‐Gaussian diffusion patterns in the prefrontal brain , 2008, Journal of magnetic resonance imaging : JMRI.

[43]  Carlos Falcón,et al.  A voxel-based diffusion tensor imaging study of temporal white matter in patients with schizophrenia , 2009, Psychiatry Research: Neuroimaging.

[44]  Yi Yan,et al.  Quantitative analysis of glioma cell invasion by diffusion tensor imaging , 2010, Journal of Clinical Neuroscience.

[45]  M. Inglese,et al.  Diffusion imaging in multiple sclerosis: research and clinical implications , 2010 .

[46]  E. Melhem,et al.  Clinical Application of MR Spectroscopy and Imaging of Brain Tumor. , 2010, Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine.

[47]  J. Helpern,et al.  Diffusional kurtosis imaging: The quantification of non‐gaussian water diffusion by means of magnetic resonance imaging , 2005, Magnetic resonance in medicine.

[48]  O. Abe,et al.  White Matter Alteration of the Cingulum in Parkinson Disease with and without Dementia: Evaluation by Diffusion Tensor Tract–Specific Analysis , 2012, American Journal of Neuroradiology.

[49]  Alessandra Bertoldo,et al.  Cortical diffusion-tensor imaging abnormalities in multiple sclerosis: a 3-year longitudinal study. , 2011, Radiology.

[50]  James M Provenzale,et al.  Multiple sclerosis: diffusion tensor MR imaging for evaluation of normal-appearing white matter. , 2002, Radiology.

[51]  C. Calli,et al.  Minimum apparent diffusion coefficients in the evaluation of brain tumors. , 2005, European journal of radiology.

[52]  R R Edelman,et al.  Time course of the apparent diffusion coefficient (ADC) abnormality in human stroke , 1997, Neurology.

[53]  U. Motosugi,et al.  High b‐Value q‐Space Analyzed Diffusion‐Weighted MRI Using 1.5 Tesla Clinical Scanner; Determination of Displacement Parameters in the Brains of Normal versus Multiple Sclerosis and Low‐Grade Glioma Subjects , 2012, Journal of Neuroimaging.

[54]  T. Nägele,et al.  Water diffusivity: comparison of primary CNS lymphoma and astrocytic tumor infiltrating the corpus callosum. , 2009, AJR. American journal of roentgenology.

[55]  Y. Cohen,et al.  Assignment of the water slow‐diffusing component in the central nervous system using q‐space diffusion MRS: Implications for fiber tract imaging , 2000, Magnetic resonance in medicine.

[56]  A. Server,et al.  Quantitative apparent diffusion coefficients in the characterization of brain tumors and associated peritumoral edema , 2009, Acta radiologica.

[57]  H. Lanfermann,et al.  Cerebral gliomas: diffusional kurtosis imaging analysis of microstructural differences. , 2010, Radiology.

[58]  Philip K. McGuire,et al.  Diffusion Tensor Imaging in Schizophrenia , 2005, Biological Psychiatry.

[59]  Y. Assaf,et al.  Diffusion Tensor Imaging (DTI)-based White Matter Mapping in Brain Research: A Review , 2007, Journal of Molecular Neuroscience.

[60]  Y. Cohen,et al.  Displacement imaging of spinal cord using q‐space diffusion‐weighted MRI , 2000, Magnetic resonance in medicine.

[61]  Jan Sijbers,et al.  Microstructural changes observed with DKI in a transgenic Huntington rat model: Evidence for abnormal neurodevelopment , 2012, NeuroImage.

[62]  J. Reichenbach,et al.  ADC changes in schizophrenia: a diffusion-weighted imaging study , 2011, European Archives of Psychiatry and Clinical Neuroscience.

[63]  Marko Wilke,et al.  Abnormal frontal white matter tracts in bipolar disorder: a diffusion tensor imaging study. , 2004, Bipolar disorders.

[64]  C. Sotak,et al.  The role of diffusion tensor imaging in the evaluation of ischemic brain injury – a review , 2002, NMR in biomedicine.

[65]  S. Aoki,et al.  A new diffusion metric, diffusion kurtosis imaging, used in the serial examination of a patient with stroke , 2012, Acta radiologica short reports.

[66]  A comparison of mean displacement values using high b-value Q-space diffusion-weighted MRI with conventional apparent diffusion coefficients in patients with stroke. , 2011, Academic radiology.

[67]  Toshinori Hirai,et al.  Usefulness of diffusion‐weighted MRI with echo‐planar technique in the evaluation of cellularity in gliomas , 1999, Journal of magnetic resonance imaging : JMRI.

[68]  H. Yamasue,et al.  Tract-specific analysis of white matter integrity disruption in schizophrenia , 2012, Psychiatry Research: Neuroimaging.

[69]  Luca Roccatagliata,et al.  MR diffusion imaging in ischemic stroke. , 2011, Neuroimaging clinics of North America.

[70]  Cheuk Y. Tang,et al.  Fronto-thalamo-striatal gray and white matter volumes and anisotropy of their connections in bipolar spectrum illnesses , 2005, Biological Psychiatry.

[71]  F. Ståhlberg,et al.  Diffusion‐weighted MRI measurements on stroke patients reveal water‐exchange mechanisms in sub‐acute ischaemic lesions , 2009, NMR in biomedicine.

[72]  Diane C. Chugani,et al.  Diffusion Tensor Imaging of Frontal Lobe in Autism Spectrum Disorder , 2008, Cerebral cortex.

[73]  q-space imaging (QSI) of the brain: comparison of displacement parameters by QSI and DWI. , 2010, Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine.

[74]  Aidos Doskaliyev,et al.  Lymphomas and glioblastomas: differences in the apparent diffusion coefficient evaluated with high b-value diffusion-weighted magnetic resonance imaging at 3T. , 2012, European journal of radiology.

[75]  H Takao,et al.  Effects of Age and Gender on White Matter Integrity , 2011, American Journal of Neuroradiology.

[76]  P. Renshaw,et al.  Update on the use of MR for assessment and diagnosis of psychiatric diseases. , 2010, Radiology.

[77]  Marco Rovaris,et al.  Assessment of normal-appearing white and gray matter in patients with primary progressive multiple sclerosis: a diffusion-tensor magnetic resonance imaging study. , 2002, Archives of neurology.

[78]  Line scan diffusion tensor MRI at low magnetic field strength: Feasibility study of cervical spondylotic myelopathy in an early clinical stage , 2006, Journal of magnetic resonance imaging : JMRI.

[79]  M Cercignani,et al.  Weekly diffusion-weighted imaging of normal-appearing white matter in MS , 2000, Neurology.