ReviewPrinciples of diffusion kurtosis imaging and its role in early diagnosis of neurodegenerative disorders
Introduction
The diagnostic use of neuroimaging has increased in the past twenty years. Different imaging techniques are widely available such as computed tomography, positron emission tomography and magnetic resonance imaging (MRI) (Smith-Bindman et al., 2012). Neuroimaging can evaluate the early development, ageing and pathological stages of the central nervous system (CNS) and monitor changes during and after treatment (Frank, 2001; Panigrahy et al., 2010; Svolos et al., 2014). MRI became an important approach in neuroscience research as well as clinical applications, due to many advantages such as wide spectrum of MRI methods used with different out comes such as strucural and diffusional methods (Johansen-Berg and Behrens, 2013), and the ability to visualize non-invasively anatomical structures of the brain or their functional state (Gierek et al., 2009). Since the brain consists of approximately 70 % of water, motion of this water throughout the tissues provides an important insight into brain microstructure. The characteristics of diffusion are often associated with the structural organization of tissues. Therefore, one rapidly developing field of MRI based on the water diffusion detection is diffusion weighted imaging (DWI). This technique was introduced fifty years ago when diffusional changes were reported for the first time (Stejskal and Tanner, 1965). DWI is a unique MRI technique which maps water motion at microstructural level and it is able to differentiate between normal and abnormal water diffusion in biological tissues (Chilla et al., 2015). DWI considers water motion free in any direction with no hindrance, i.e. isotropic diffusion. DWI is widely used in clinical fields, in diagnosis of acute ischemic stroke, traumatic brain injury and inflammation (Ulug et al., 1997; Fung et al., 2011). However, all biological systems are complex structures with a variety of barriers restricting the water diffusion and leading to directional water movement. This process is called anisotropic diffusion (Chilla et al., 2015).
Section snippets
Physical theory of the diffusion weighted imaging
Diffusion is a mass transport, a random movement of molecules or particles (which do not require bulk motion) (Basser, 1995; Basser and Pierpaoli, 2011). An approach to diffusion was undertaken by Einstein and Smoluchowski, they proposed a displacement distribution parameter describing the mean squared displacement of the particles in timeframe (Einstein 1905).where D is diffusion coefficient, <x2> is the mean squared displacement during a diffusion time Δ. In three-dimension, the
Diffusion tensor imaging (DTI)
The biological organized structure of the CNS including myelinated axons, unmyelinated axons, cellular membrane, presence of proteins and intracellular organelles affect the water diffusion inside the CNS. These factors could divide the water diffusion in CNS into two types, isotropic diffusion in which water diffusion is equal in all directions and is observed in cerebrospinal fluid and grey matter. The second type is anisotropic diffusion, in which water diffusion is mostly unidirectional and
Diffusion kurtosis imaging (DKI)
DTI considers the diffusion of water in brain as Gaussian distribution, hence it is unable to detect the diffusion heterogeneity in biological tissues. Therefore, DKI technique was introduced as a mathematical extension of DTI. Kurtosis is described as a dimensionless measure which quantifies the non-Gaussian distribution of water diffusion in a voxel (Jensen et al., 2005; Jensen and Helpern, 2010). Thus, DKI also considers the voxel in the biological system as a bucket of water but with
Parkinson’s disease
Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder characteristic by motor symptoms represented by bradykinesia, resting tremor, muscle rigidity and gait problems. The PD patients also suffer numerous non-motor symptoms including cognitive dysfunction, sleep disorders, psychiatric comorbidities, olfactory and gastrointestinal dysfunctions (Chaudhuri and Martinez-Martin, 2008). Furthermore, motor PD symptoms start when 50–70 % of dopaminergic projections
Conclusion
The importance of early diagnosis in neurodegeneration is of paramount importance for the future development of neuroprotective treatments. Furthermore, such approach helps in better understanding of the mechanisms which underlay the pathology. Based on the studies we reviewed, changes in DKI matrices reflects the structural complexity which may occur due to neuroinflammation such as immune activation and protein accumulation. Additionally, DKI showed a remarkable effect in detecting the
Conflict of interest statement
All authors declare no conflict of interest.
Acknowledgements
This paper was written at Masaryk University as a part of the project „Behavioral psychopharmacology and pharmacokinetics in preclinical drug research“, number MUNI/A/1132/2017, with the support of the Specific University Research Grant, as provided by the Ministry of Education, Youth and Sports of the Czech Republic in the year 2018.
References (84)
- et al.
Diffusion tensor imaging of the brain
Neurotherapeutics
(2007) - et al.
Recollections about our 1996 JMR paper on diffusion anisotropy
J. Magn. Reson.
(2011) - et al.
Identification and characterization of Huntington related pathology: an in vivo DKI imaging study
Neuroimage
(2012) - et al.
Quantitative diffusion tensor imaging detects dopaminergic neuronal degeneration in a murine model of Parkinson's disease
Neurobiol. Dis.
(2007) - et al.
Staging of brain pathology related to sporadic Parkinson's disease
Neurobiol. Aging
(2003) - et al.
Diffusion tensor imaging in hemorrhagic stroke
Exp. Neurol.
(2015) - et al.
Immunolocalization of human alpha-synuclein in the Thy1-aSyn (Line 61) transgenic mouse line
Neuroscience
(2014) - et al.
Non-Gaussian diffusion MRI assessment of brain microstructure in mild cognitive impairment and Alzheimer's disease
Magn. Reson. Imaging
(2013) - et al.
MR diffusion imaging in ischemic stroke
Neuroimaging Clin. N. Am.
(2011) - et al.
Magnetic resonance tractography in neuroradiological diagnostic aspects
Otolaryngol. Pol.
(2009)
Therapeutic strategies for Alzheimer's disease in clinical trials
Pharmacol. Rep.
Correlations between microstructural alterations and severity of cognitive deficiency in Alzheimer's disease and mild cognitive impairment: a diffusional kurtosis imaging study
Magn. Reson. Imaging
Amyloid-induced neurofibrillary tangle formation in Alzheimer's disease: insight from transgenic mouse and tissue-culture models
Int. J. Dev. Neurosci.
Diffusion kurtosis imaging probes cortical alterations and white matter pathology following cuprizone induced demyelination and spontaneous remyelination
Neuroimage
Diffusional kurtosis imaging of cingulate fibers in Parkinson disease: comparison with conventional diffusion tensor imaging
Magn. Reson. Imaging
Early and progressive microstructural brain changes in mice overexpressing human alpha-synuclein detected by diffusion kurtosis imaging
Brain Behav. Immun.
Abnormalities of the uncinate fasciculus and posterior cingulate fasciculus in mild cognitive impairment and early Alzheimer's disease: a diffusion tensor tractography study
Brain Res.
Inflammatory responses to amyloidosis in a transgenic mouse model of Alzheimer's disease
Am. J. Pathol.
Update on diffusion MRI in Parkinson's disease and atypical parkinsonism
J. Neurol. Sci.
Basic principles and concepts underlying recent advances in magnetic resonance imaging of the developing brain
Semin. Perinatol.
Diffusion tensor MR imaging
Neuroimaging Clin. N. Am.
Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data
Neuroimage
Huntington's disease
Lancet
Quantitative histological analysis of amyloid deposition in Alzheimer's double transgenic mouse brain
Neuroscience
Processing and visualization for diffusion tensor MRI
Med. Image Anal.
Diffusion kurtosis as an in vivo imaging marker for reactive astrogliosis in traumatic brain injury
Neuroimage
A geometric analysis of diffusion tensor measurements of the human brain
Magn. Reson. Med.
Alpha-synuclein cell-to-cell transfer and seeding in grafted dopaminergic neurons in vivo
PLoS One
Assignment of the water slow-diffusing component in the central nervous system using q-space diffusion MRS: implications for fiber tract imaging
Magn. Reson. Med.
Inferring microstructural features and the physiological state of tissues from diffusion-weighted images
NMR Biomed.
New histological and physiological stains derived from diffusion-tensor MR images
Ann. N. Y. Acad. Sci.
The connection between MCI and Alzheimer disease: neurocognitive clues
Turk. J. Med. Sci.
Development of Alzheimer-related neurofibrillary changes in the neocortex inversely recapitulates cortical myelogenesis
Acta Neuropathol.
Case control study of diffusion tensor imaging in Parkinson's disease
J. Neurol. Neurosurg. Psychiatry
Quantitation of non-motor symptoms in Parkinson's disease
Eur. J. Neurol.
Diffusion weighted magnetic resonance imaging and its recent trend-a survey
Quant. Imaging Med. Surg.
New MRI markers for Alzheimer's disease: a meta-analysis of diffusion tensor imaging and a comparison with medial temporal lobe measurements
J. Alzheimers Dis.
Diffusion tensor imaging in parkinsonian syndromes: a systematic review and meta-analysis
Neurology
Inclusion formation and neuronal cell death through neuron-to-neuron transmission of alpha-synuclein
Proc. Natl. Acad. Sci. U. S. A.
Diffusion tensor imaging findings in semi-acute mild traumatic brain injury
J. Neurotrauma
Über die von der molekularkinetischen Theorie der Wärme geforderte Bewegung von in ruhenden Flüssigkeiten suspendierten Teilchen
Annalen der Physik
Age-related non-Gaussian diffusion patterns in the prefrontal brain
J. Magn. Reson. Imaging
Cited by (68)
Neuroimaging in early-treated phenylketonuria patients and clinical outcome: A systematic review
2023, Molecular Genetics and MetabolismNeuroimaging-Derived Biomarkers of the Antidepressant Effects of Ketamine
2023, Biological Psychiatry: Cognitive Neuroscience and NeuroimagingIn vivo Correlation Tensor MRI reveals microscopic kurtosis in the human brain on a clinical 3T scanner
2022, NeuroImageCitation Excerpt :DKI quantifies the excess-kurtosis in water displacement probability which can be used as an index of diffusion non-Gaussianity, which presumably reflects the heterogeneity of the diffusion process in tissue microstructure (Jensen et al., 2005; Jensen and Helpern, 2010; Wu and Cheung, 2010). DKI has been successfully adopted to study both the healthy and the diseased human brain, providing insights into individual anatomical details at high resolution (Mohammadi et al., 2015), development (Huber et al., 2019), ageing (Falangola et al., 2008; Henriques, 2018), attention deficit hyperactivity disorder (ADHD, Helpern et al., 2011), neurodegenerative disorders (Arab et al., 2018) such as Alzheimer's (Gong et al., 2013; Struyfs et al., 2015) and Parkinson's disease (Wang et al., 2011; Kamagata et al., 2013, 2014; Surova et al., 2018), and brain tumors (Raab et al., 2010; Raja et al., 2016; Delgado et al., 2018; Hempel et al., 2017, 2018; Lin et al., 2018). Indeed, DKI is nowadays implemented on many different imaging platforms (e.g. Leemans et al., 2009; Tabesh et al., 2011; Tournier et al., 2019; Henriques et al., 2021a).