Q-space Imaging Research Articles

Multiple sclerosis: Benefits of q-space imaging in evaluation of normal-appearing and periplaque white matter

IntroductionDiffusion tensor imaging (DTI) reveals white matter pathology in patients with multiple sclerosis (MS). A recent non-Gaussian diffusion imaging technique, q-space imaging (QSI), may provide several advantages over conventional MRI techniques in regard to in vivo evaluation of the disease process in patients with MS. The purpose of this study is to investigate the use of root mean square displacement (RMSD) derived from QSI data to characterize plaques, periplaque white matter (PWM), and normal-appearing white matter (NAWM) in patients with MS. MethodsWe generated apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps by using conventional DTI data from 21 MS patients; we generated RMSD maps by using QSI data from these patients. We used the Steel–Dwass test to compare the diffusion metrics of regions of interest in plaques, PWM, and NAWM. ResultsADC differed (P<0.05) between plaques and PWM and between plaques and NAWM. FA differed (P<0.05) between plaques and NAWM. RMSD differed (P<0.05) between plaques and PWM, plaques and NAWM, and PWM and NAWM. ConclusionRMSD values from QSI may reflect microstructural changes and white-matter damage in patients with MS with higher sensitivity than do conventional ADC and FA values.

Seasonal Changes in the Dynamic State of Water for Excised Cherry Branches (Prunus lannesiana) Observed Using Dedicated Micro-Magnetic Resonance Imaging

Seasonal changes in the dynamic state of water for cherry (Prunus lannesiana), a deciduous broad-leaved tree, were studied by combined k-space and q-space imaging using dedicated magnetic resonance imaging (MRI) with a 1.0-T permanent magnet. Water amounts, diffusion coefficients and transpiration were examined for excised branches cut from a tree with and without weak light (100–140 μmol m-2 s-1) throughout the year. The water amount in the cambium was large in spring and summer, decreased in autumn, and decreased further in winter. There were three components in the diffusion coefficient of the branch. The second component of the diffusion coefficient ascribed to the cambium did not fluctuate notably throughout the year, despite marked alternation in water amounts. However, diffusion coefficients in the secondary xylem, the primary component, were elevated in summer and decreased in winter. Upward water flow was restricted in the secondary xylem, and the positions where large flow was detected coincided with places exhibiting high diffusion coefficients and the arrangements of vessels. Total transpiration exhibited a tendency similar to that of the diffusion coefficients; however, total transpiration declined to zero when the plant had no leaf, whereas the diffusion coefficient decreased to 60 % of the maximum but did not decrease further. Light-enhanced transpiration related to potential photosynthetic activity increased in spring as the leaves sprouted and grew, considerably decreased in summer, decreased to one third of the maximum in autumn, and was not detected in winter. Measurement of the dynamic state of water for the excised branches will provide useful information for better understanding of the phenological changes of tree physiology.

Diffusion MR Imaging of White Matter Pathways

Diffusion tensor imaging (DTI) is one of the most promising MRI techniques for characterizing microstructural changes of cerebral white matter in brain research and clinical applications. The number of DTI studies is increasing, and more than 7500 articles have been published over the last decade. DTI enables visualization and characterization of white matter tracts in vivo by providing a unique image contrast on white matter that is unavailable with routine MR techniques; this allows three-dimensional (3D) visualization of neuronal pathways and quantification of the diffusion properties of white matter. Since its introduction in 1994, DTI has been used to study the structure of white matter and changes to its integrity within normal brains and brains affected by aging, stroke, dementia, psychiatric disorder, tumor, and other conditions. In this paper, the technical aspects and clinical applications of DTI are reviewed with a focus on clinical use and in vivo studies. The strengths and weaknesses of the approach are discussed and current extensions of the technology (q-space imaging and diffusional kurtosis imaging) are summarized.

Dynamic State of Water in Excised Ligustrum Lucidum Branches Observed by Dedicated Micro-Magnetic Resonance Imaging

The dynamic state of water was investigated for tree branches by a combined k-space and q-space imaging method using a dedicated magnetic resonance imaging (MRI) device equipped with a 1.0-T permanent magnet. Changes in the 1H-NMR image due to the application of pulsed-field gradients (PFG) of stepping magnitude were measured using a phantom consisting of flow water and stationary water; the relationship between the flow velocities and the diffusion coefficients of water was studied. The method was applied to excised Ligustrum lucidum branches under conditions with and without weak light (100-140 μmol m-2 s-1). The distributions and diffusion coefficients of cell-associated water for individual tissues in the branches were determined in relation to morphology. Large amounts of water existed but diffusion coefficients were not high in the cambium. Though the water amounts were moderate, the highest diffusion coefficient exceeded that for pure water in the secondary xylem. The conduit tubes were smaller than the imaging pixel, unlike the phantom, so the determined values might be perturbed by the conditions of the ambient cell-associated water. However, positional responses in the xylem flow to light were detected, and a flow velocity up to 0.71 mm s-1 by transpiration was recorded. The movement of water in the phloem was not distinguished from large amounts of water in adjacent tissues, probably due to the very small cells and slow rates of flow in the phloem.

Non‐gaussian diffusion‐weighted imaging for assessing diurnal changes in intervertebral disc microstructure

To investigate the use of non-Gaussian diffusion-weighted imaging (q-space imaging [QSI]) to estimate diurnal changes in intervertebral disc (IVD) microstructure. IVDs of 15 male subjects (mean age, 27.3 years; mean body mass index, 22.50 kg/m(2) ) were investigated once in the morning, less than 30 min after rising, and a second time in the evening after at least 10 h of normal physical activity, using 3 Tesla (T) MR imaging. T2 mapping and QSI data values (apparent diffusion coefficient [ADC], root mean square displacement [RMSD], and apparent kurtosis coefficient [AKC]) were calculated and compared between the morning and evening imaging sessions. The T2, ADC, and RMSD values showed a significant decrease in the evening (175.8 ± 49.5 ms, 1.56 ± 0.32 10(-3) mm(2) /s and 40.0 ± 3.0 μm, respectively; P < 0.05 for all values; paired t-test), when compared with the morning values (226.5 ± 83.8 ms, 1.69 ± 0.29 10(-3) mm(2) /s and 45.2 ± 2.9 μm, respectively). The AKC value showed a significant increase in the evening (0.67 ± 0.08), when compared with the morning value (0.58 ± 0.04; P < 0.05). The RMSD and AKC values obtained from QSI analysis may be biomarkers for IVD diurnal microstructural changes.

Neuroimaging biomarkers for epilepsy: Advances and relevance to glial cells

Glial cells play an important role in normal brain function and emerging evidence would suggest that their dysfunction may be responsible for some epileptic disease states. Neuroimaging of glial cells is desirable, but there are no clear methods to assess neither their function nor localization. Magnetic resonance imaging (MRI) is now part of a standardized epilepsy imaging protocol to assess patients. Structural volumetric and T2-weighted imaging changes can assist in making a positive diagnosis in a majority of patients. The alterations reported in structural and T2 imaging is predominately thought to reflect early neuronal loss followed by glial hypertrophy. MR spectroscopy for myo-inositol is a being pursued to identify glial alterations along with neuronal markers. Diffusion weighted imaging (DWI) is ideal for acute epileptiform events, but is not sensitive to either glial cells or neuronal long-term changes found in epilepsy. However, DWI variants such as diffusion tensor imaging or q-space imaging may shed additional light on aberrant glial function in the future. The sensitivity and specificity of PET radioligands, including those targeting glial cells (translocator protein) hold promise in being able to image glial cells. As the role of glial function/dysfunction in epilepsy becomes more apparent neuroimaging methods will evolve to assist the clinician and researcher in visualizing their location and function.

Associations among q-space MRI, diffusion-weighted MRI and histopathological parameters in meningiomas

The purposes of this MR-based study were to calculate q-space imaging (QSI)-derived mean displacement (MDP) in meningiomas, to evaluate the correlation of MDP values with apparent diffusion coefficient (ADC) and to investigate the relationships among these diffusion parameters, tumour cell count (TCC) and MIB-1 labelling index (LI). MRI, including QSI and conventional diffusion-weighted imaging (DWI), was performed in 44 meningioma patients (52 lesions). ADC and MDP maps were acquired from post-processing of the data. Quantitative analyses of these maps were performed by applying regions of interest. Pearson correlation coefficients were calculated for ADC and MDP in all lesions and for ADC and TCC, MDP and TCC, ADC and MIB-1 LI, and MDP and MIB-1 LI in 17 patients who underwent subsequent surgery. ADC and MDP values were found to have a strong correlation: r = 0.78 (P = <0.0001). Both ADC and MDP values had a significant negative association with TCC: r = -0.53 (p = 0.02) and -0.48 (P = 0.04), respectively. MIB-1 LI was not, however, found to have a significant association with these diffusion parameters. In meningiomas, both ADC and MDP may be representative of cell density. • Diffusion-weighted MRI offers possibilities to assess the aggressiveness of meningiomas. • The q-space imaging-derived mean displacement correlates strongly with apparent diffusion coefficients. • Both diffusion parameters showed a strong negative association with tumour cell counts. • Derived mean displacement may help assess the aggressiveness of meningiomas preoperatively.

Detection of early neuronal damage in CADASIL patients by q-space MR imaging

q-Space imaging is a novel magnetic resonance (MR) technique that enables the assessment of ultrastructural changes of white matter. We hypothesized that this technique would facilitate the assessment of the progressive nature of neuronal damage seen in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). This study was approved by the institutional review board. Seven consecutive adult patients (five men and two women) with the CADASIL gene mutation were studied. Two patients were preclinical cases without overt episodes of stroke. The control group consisted of five normal volunteers. All MR examinations were performed using a 1.5-T whole-body imager. q-Space imaging was performed using a single-shot, echo-planar imaging technique and Δ/δ = 142/17 ms. Gradient magnitudes were increased in nine steps to reach a maximal b value of 10,000 s/mm². Total acquisition time of q-space imaging was 25 min. The ADC maps calculated from the b = 1,000 images were used for comparisons. Both q-space imaging and ADC maps depicted progressive neuronal damage. Early neuronal damage was especially well depicted using q-space imaging, with preferential involvement of the frontal lobes and central gray matters. Later progression was better depicted by b = 1,000 ADC maps at the temporal lobes. Visual assessment of images revealed a trend for occipital lobe sparing, especially on q-space imaging. q-Space imaging demonstrated early neuronal damage in a characteristic distribution. Since this method appears to be sensitive to early neuronal damage, it could conceivably aid in monitoring patients in the preclinical stage and may help in assessing the effects of future medical interventions.

Age-related white matter changes in high b-value q-space diffusion-weighted imaging

To assess and compare age-related diffusion changes in the white matter in different cerebral lobes, as quantified by diffusion-weighted imaging (DWI) and high b-value q-space imaging (QSI). Seventy-three cases without neurological symptoms or imaging abnormalities were grouped by age as young (<30 years, n = 20), middle-aged (30-49 years, n = 19), old (50-69 years, n = 18), and very old (> 70 years, n = 16) and imaged by a 1.5-T MR scanner for DWI and QSI. Apparent diffusion coefficient (ADC) and mean displacement (MDP) values were calculated in the white matter of frontal, parietal, and temporal lobes and compared using Dunnett's test, with the young group as a control. MDP values in frontal and parietal lobes were significantly higher in old and very old age groups than in the young, while those in the temporal lobes were significantly higher only in the very old group. ADC values were significantly higher in all three lobes in the very old group. QSI is more sensitive than DWI to age-related myelin loss in white matter.

High‐Level Gait Disorder: Associations with Specific White Matter Changes Observed on Advanced Diffusion Imaging

High-level gait disorder (HLGD) is a debilitating disorder causing mobility decline in the elderly. Although its clinical characteristics are well described, its anatomical and pathophysiological underpinnings are poorly understood. This study examined the anatomical distribution of white matter (WM) changes in patients with mild to moderate HLGD of the cautious/disequilibrium type, using advanced magnetic resonance imaging (MRI) methods. Thirteen patients with HLGD, 9 elderly and 13 middle-aged healthy controls were scanned using diffusion tensor imaging, Q-space imaging, and conventional MRI. The regions of significant differences between the HLGD group and the elderly control group were defined, and the mean fractional anisotropy and displacement values of these areas were extracted. The HLGD patients had lower fractional anisotropy and higher displacement values in regions related to the motor system, including those along the corticospinal tract and the superior cerebellar peduncles, as well as in cognitive and affective-related areas, including the anterior limbs of the internal capsule and the genu of the corpus callosum. The anatomical distribution associated with HLGD of the cautious/disequilibrium type involves WM pathways that convey motor-related, cognitive and affective-related functions. The underlying pathological process leading to these changes most probably includes demyelination.

New diffusion metrics for spondylotic myelopathy at an early clinical stage

ObjectivesTo investigate the use of root mean square displacement (RMSD) and mean diffusional kurtosis (DK) metrics of q-space imaging data to estimate spinal cord compression in patients with early cervical spondylosis.MethodsWe studied 50 consecutive patients at our institution (22 male, 28 female; mean age 58 years; age range 20–86 years) who had clinical signs and symptoms suggestive of early clinical stage cervical myelopathy. After conventional magnetic resonance (MR) imaging, diffusion tensor and q-space image data were acquired using 3-T MR imaging. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), RMSD and mean DK values were calculated and compared between compressed and uncompressed spinal cords.ResultsFA and mean DK values were significantly lower and RMSD was significantly higher (P = 0.0060, 0.0020 and 0.0062, respectively; Mann–Whitney U test with the Bonferroni correction) in compressed spinal cords than in uncompressed cords. ADC was also higher in compressed cords, but this difference was not statistically significant.ConclusionsIn the evaluation of spinal cord damage in early cervical spondylosis, mean DK and RMSD values in the spinal cord may be highly sensitive indicators of microstructural change and damage.Key Points• Absolute surgical indications for cervical spondylosis with myelopathy remain to be established.• Diffusion tensor MRI shows abnormalities in normal-appearing but compressed spinal cord.• Non-Gaussian diffusion analysis is highly sensitive in revealing spinal cord damage.

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.

Mean displacement map of spine and spinal cord disorders using high b-value q-space imaging-feasibility study

Q-space analysis is a new metric that uses multiple, high b-value, diffusion-weighted magnetic resonance (MR) data. This technique shows promising results as a tool to provide information complementary to that of other imaging techniques used on biological tissue in vivo. To investigate the use of a mean displacement (MDP) map of high b-value, q-space imaging (QSI) to characterize spinal and spinal cord lesions in vivo. Eight patients with spine or spinal cord disorders (two neurinomas, one myeloma, three cases of syringohydromyelia, and two cases of cervical spondylosis) were included. The MR imaging protocol consisted of conventional MR sequences, conventional diffusion-weighted imaging (DWI; b = 1000), and high b-value QSI with a maximum q value of 836.9 cm(-1). Apparent diffusion coefficient (ADC) maps of conventional DWI and MDP maps of QSI data were obtained and region-of-interest analyses for the lesions were performed. MDP values of normal spinal cord, cerebrospinal fluid (CSF), and tumor parenchyma were 6.57 ± 0.52, 17.6 ± 2.75, and 8.49 ± 2.09, respectively (µm, mean ± standard deviation). In general, MDP maps were not well correlated with the corresponding ADC maps at the pathologic lesions. Spondylotic lesions tended to have higher MDP values than normal spinal cord, whereas syringohydromyelia produced MDP values slightly lower than those of CSF. The heterogeneous MDP values were probably due to differences in tissues and pathologic structures. This technique has potential to provide additional clinical information to that obtained with conventional MR imaging.

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

We aimed to determine the displacement parameters in the brains of normal individuals relative to brain parenchymal abnormalities, such as multiple sclerosis (MS) and low-grade glioma, by q-space imaging (QSI) using 1.5-T magnetic resonance (MR) scanner. Thirty-five normal, three pathologically proven low-grade glioma, and five MS subjects were imaged by a 1.5-T MR unit for QSI (b-values, 0-12,000 s/mm(2)). Mean displacement (MD) values in white matter (WM), gray matter (GM), and lateral ventricle (cerebrospinal fluid [CSF]) of normal subjects, plaques, and normal appearing WM (NAWM) of MS subjects and glioma lesions were calculated. Mann-Whitney U test was used for comparison. In normal subjects, MD values were 6.6 ± 0.2, 8.44 ± 0.41, and 17.08 ± 0.80 μm for WM, GM, and CSF, respectively, while those for NAWM and WM plaques in MS, and glioma lesions were significantly higher at 7.0 ± 0.17, 9.3 ± 2.3, and 9.6 ± 0.40 μm, respectively, compared to WM in normal subjects. We propose that the relative values of MD obtained by QSI in control and diseased tissues can be useful for diagnosing various WM abnormalities.

Estimation of fiber orientation and spin density distribution by diffusion deconvolution

A diffusion deconvolution method is proposed to apply deconvolution to the diffusion orientation distribution function (dODF) and calculate the fiber orientation distribution function (fODF), which is defined as the orientation distribution of the fiber spin density. The dODF can be obtained from q-space imaging methods such as q-ball imaging (QBI), diffusion spectrum imaging (DSI), and generalized q-sampling imaging (GQI), and thus the method can be applied to various diffusion sampling schemes. A phantom study was conducted to compare the angular resolution of the fODF with the dODF, and the in vivo datasets were acquired using single-shell, two-shell, and grid sampling schemes, which were then reconstructed by QBI, GQI, and DSI, respectively. The phantom study showed that the fODF significantly improved the angular resolution over the dODF at 45- and 60-degree crossing angles. The in vivo study showed consistent fODF regardless of the applied sampling schemes and reconstruction methods, and the ability to resolve crossing fibers was improved in reduced sampling condition. The fiber spin density obtained from deconvolution showed a higher contrast-to-noise ratio than the fractional anisotropy (FA) mapping, and further application on tractography showed that the fiber spin density can be used to determine the termination of fiber tracts. In conclusion, the proposed deconvolution method is generally applicable to different q-space imaging methods. The calculated fODF improves the angular resolution and also provides a quantitative index of fiber spin density to refine fiber tracking.

Water diffusion in q-space imaging as a probe of cell local viscosity and anomalous diffusion in grey and white matter

Water diffusion in q-space imaging as a probe of cell local viscosity and anomalous diffusion in grey and white matter

Quantifying axon diameter and intra-cellular volume fraction in excised mouse spinal cord with q-space imaging

Q-space magnetic resonance imaging (QSI) can quantify white matter (WM) axonal architecture at the cellular level non-destructively, unlike histology, but currently has several limitations. First, current methodology does not differentiate between diffusing molecules occupying extra- or intra-cellular spaces (ECS and ICS, respectively). Second, accurate assessment of axonal architecture requires high-gradient amplitudes not clinically available. Third, the only direct QSI marker of axonal architecture has been mean axon diameter (MAD), even though other direct markers would be valuable as well. The objective was to investigate three QSI-based methods that address the above limitations. Method 1 employs a two-compartment model to account for signal from ECS and ICS. Method 2 uses data only from low q-values thereby obviating the need for high-gradient amplitudes. Method 3 empirically estimates ICS volume fraction and provides an additional metric of axonal architecture. We implemented each method on data from excised healthy adult mouse spinal cords collected previously using a home-built 50T/m z-gradient yielding sub-micron displacement resolution. Through comparison with histology, each method was evaluated for accuracy in assessing axonal architecture. MAD measured with Methods 1 and 2 showed good correlation with histology (R2=0.99 (p<0.0001), and 0.77 (p<0.01), respectively) and Bland–Altman analysis indicates that measurements from the two methods are not significantly different from histology. The third method measured ICS volume fractions (0.64±0.07) that were highly correlated (R2=0.92, p<0.05) with measurements from histology (0.68±0.07). These methods may provide insight into axonal architecture in normal and abnormal WM tissue but additional validation with more samples will be needed.

Q-space Imaging (QSI) of the Brain: Comparison of Displacement Parameters by QSI and DWI

q-space Imaging (QSI) of the Brain: Comparison of Displacement Parameters by QSI and DWI

Helium-3 MR q-space imaging with radial acquisition and iterative highly constrained back-projection.

An undersampled diffusion-weighted stack-of-stars acquisition is combined with iterative highly constrained back-projection to perform hyperpolarized helium-3 MR q-space imaging with combined regional correction of radiofrequency- and T1-related signal loss in a single breath-held scan. The technique is tested in computer simulations and phantom experiments and demonstrated in a healthy human volunteer with whole-lung coverage in a 13-sec breath-hold. Measures of lung microstructure at three different lung volumes are evaluated using inhaled gas volumes of 500 mL, 1000 mL, and 1500 mL to demonstrate feasibility. Phantom results demonstrate that the proposed technique is in agreement with theoretical values, as well as with a fully sampled two-dimensional Cartesian acquisition. Results from the volunteer study demonstrate that the root mean squared diffusion distance increased significantly from the 500-mL volume to the 1000-mL volume. This technique represents the first demonstration of a spatially resolved hyperpolarized helium-3 q-space imaging technique and shows promise for microstructural evaluation of lung disease in three dimensions.

Der Beitrag neuer MRT-Untersuchungs- und Analysetechniken

Routine MRI is a key element in the diagnosis and differential diagnosis of MS. Conventional MRI contrasts are very commonly used as adjuncts to the clinical and neurophysiological assessment of the patient status in the course of the disease. Background information from MRI frequently offers the best opportunity to provide an individual understanding and concept of the patients disease and provides a basis for a treatment rationale. Beyond the visualisation of the groß pathology on brain MRI imaging of the spinal cord is acknowledged as an area of great importance, however it is technically challenging and therefore its use is more limited. New technical opportunities allow the fast visualisation of the whole cord. We have employed a fast biplanar MRI approach of the whole cord as a routine examination, which can be very helpful to ascertain cord pathology. Another area where MRI can be useful is the detection and quantification of tissue changes that are not easily accessible to the eye. Subtle changes are known to occur in the NAWM of MS patients, including diffuse astrocytic hyperplasia, patchy edema, perivascular infiltration, gliosis, abnormally thin myelin and axonal loss. It is also evident from pathological studies that frequently a slowly progressive axonal loss leeds to brain atrophy. Atrophy assessment becomes increasingly more sophisticated and new quantitative MRI techniques (Q-space diffusion imaging) may open new avenues to also assess the less overt pathological changes in MS. We have recently used Q-space imaging that demonstrates a high sensitivity to detect reductions of the slow diffusion component in the NAWM of patients with different MS types. Color coding of resulting calculated maps of the „Probability of Zero Displacement“ (PZD) show areas of loss of the slow diffusion component quite obviously making it also accessible to a qualitative analysis approach. Such additional information maybe of value for the clinician when the clinical status of the patient is still functionally well compensated in a low EDSS range but more objective information on morphological changes are useful.