Accelerated Diffusion Basis Spectrum Imaging With Tensor Computations

Diffusion basis spectrum imaging (DBSI) has shown promise in evaluating cervical spinal cord structural changes in patients with cervical spondylotic myelopathy (CSM). DBSI may also be valuable in the postoperative setting by serially tracking spinal cord microstructural changes following decompressive cervical spine surgery. Currently, there is a paucity of studies investigating this topic, likely because of challenges in resolving signal distortions from spinal instrumentation. Therefore, the objective of this study was to assess the feasibility of DBSI metrics extracted from the C3 spinal level to evaluate CSM patients postoperatively. Fifty CSM patients and 20 healthy controls were enrolled in a single-center prospective study between 2018 and 2020. All patients and healthy controls underwent preoperative and postoperative diffusion-weighted MRI (dMRI) at a 2-year follow-up. All CSM patients underwent decompressive cervical surgery. The modified Japanese Orthopaedic Association (mJOA) score was used to categorize CSM patients as having mild, moderate, or severe myelopathy. DBSI metrics were extracted from the C3 spinal cord level to minimize image artifact and reduce partial volume effects. DBSI anisotropic tensors evaluated white matter tracts through fractional anisotropy, axial diffusivity, radial diffusivity, and fiber fraction. DBSI isotropic tensors assessed extra-axonal pathology through restricted and nonrestricted fractions. Of the 50 CSM patients, both baseline and postoperative dMR images with sufficient quality for analysis were obtained in 27 patients. These included 15 patients with mild CSM (mJOA scores 15-17), 7 with moderate CSM (scores 12-14), and 5 with severe CSM (scores 0-11), who were followed up for a mean of 23.5 (SD 4.1, range 11-31) months. All preoperative C3-level DBSI measures were significantly different between CSM patients and healthy controls (p < 0.05), except DBSI fractional anisotropy (p = 0.31). At the 2-year follow-up, the same significance pattern was found between CSM patients and healthy controls, except DBSI radial diffusivity was no longer statistically significant (p = 0.75). When assessing change (i.e., postoperative - preoperative values) in C3-level DBSI measures, CSM patients exhibited significant decreases in DBSI radial diffusivity (p = 0.02), suggesting improvement in myelin integrity (i.e., remyelination) at the 2-year follow-up. Among healthy controls, there was no significant difference in DBSI metrics over time. DBSI metrics derived from dMRI at the C3 spinal level can be used to provide meaningful insights into representations of the spinal cord microstructure of CSM patients at baseline and 2-year follow-up. DBSI may have the potential to characterize white matter tract recovery and inform outcomes following decompressive cervical surgery for CSM.

Using diffusion basis spectrum imaging (DBSI) to examine the microstructural changes in the substantia nigra (SN) and global white matter (WM) tracts of patients with early-stage PD. Thirty-seven age- and sex-matched patients with early-stage PD and 22 healthy controls (HCs) were enrolled in this study. All participants underwent clinical assessments and diffusion-weighted MRI scans, analyzed by diffusion tensor imaging (DTI) and DBSI to assess the pathologies of PD in SN and global WM tracts. The lower DTI fraction anisotropy (FA) was seen in SN of PD patients (PD: 0.316 ± 0.034 vs HCs: 0.331 ± 0.019, p = 0.015). The putative cells marker-DBSI-restricted fraction (PD: 0.132 ± 0.051 vs HCs: 0.105 ± 0.039, p = 0.031) and the edema/extracellular space marker-DBSI non-restricted-fraction (PD: 0.150 ± 0.052 vs HCs: 0.122 ± 0.052, p = 0.020) were both significantly higher and the density of axons/dendrites marker-DBSI fiber-fraction (PD: 0.718 ± 0.073 vs HCs: 0.773 ± 0.071, p = 0.003) was significantly lower in SN of PD patients. DBSI-restricted fraction in SN was negatively correlated with HAMA scores (r = - 0.501, p = 0.005), whereas DTI-FA was not correlated with any clinical scales. In WM tracts, only higher DTI axial diffusivity (AD) among DTI metrics was found in multiple WM regions in PD, while lower DBSI fiber-fraction and higher DBSI non-restricted-fraction were detected in multiple WM regions. DBSI non-restricted-fraction in both left fornix (cres)/stria terminalis (r = -0.472, p = 0.004) and right posterior thalamic radiation (r = - 0.467, p = 0.005) was negatively correlated with MMSE scores. DBSI could potentially detect and quantify the extent of inflammatory cell infiltration, fiber/dendrite loss, and edema in both SN and WM tracts in patients with early-stage PD, a finding remains to be further investigated through more extensive longitudinal DBSI analysis. Our study shows that DBSI indexes can potentially detect early-stage PD's pathological changes, with a notable ability to distinguish between inflammation and edema. This implies that DBSI has the potential to be an imaging biomarker for early PD diagnosis. • Diffusion basis spectrum imaging detected higher restricted-fraction in Parkinson's disease, potentially reflecting inflammatory cell infiltration. • Diffusion basis spectrum imaging detected higher non-restricted-fraction and lower fiber-fraction in Parkinson's disease, indicating the presence of edema and/or dopaminergic neuronal/dendritic loss. • Diffusion basis spectrum imaging metrics correlated with non-motor symptoms, suggesting its potential diagnostic role to detect early-stage PD dysfunctions.

Diffusion basis spectrum imaging (DBSI) is a noninvasive quantitative imaging modality that may improve understanding of cervical spondylotic myelopathy (CSM) pathology through detailed evaluations of spinal cord microstructural compartments. To determine the utility of DBSI as a biomarker of CSM disease severity. A single-center prospective cohort study enrolled 50 patients with CSM and 20 controls from 2018 to 2020. All patients underwent clinical evaluation and diffusion-weighted MRI, followed by diffusion tensor imaging and DBSI analyses. Diffusion-weighted MRI metrics assessed white matter integrity by fractional anisotropy, axial diffusivity, radial diffusivity, and fiber fraction. In addition, DBSI further evaluates extra-axonal changes by isotropic restricted and nonrestricted fraction. Including an intra-axonal diffusion compartment, DBSI improves estimations of axonal injury through intra-axonal axial diffusivity. Patients were categorized into mild, moderate, and severe CSM using modified Japanese Orthopedic Association classifications. Imaging parameters were compared among patient groups using independent samples t tests and ANOVA. Twenty controls, 27 mild (modified Japanese Orthopedic Association 15-17), 12 moderate (12-14), and 11 severe (0-11) patients with CSM were enrolled. Diffusion tensor imaging and DBSI fractional anisotropy, axial diffusivity, and radial diffusivity were significantly different between control and patients with CSM ( P < .05). DBSI fiber fraction, restricted fraction, and nonrestricted fraction were significantly different between groups ( P < .01). DBSI intra-axonal axial diffusivity was lower in mild compared with moderate (mean difference [95% CI]: 1.1 [0.3-2.1], P < .01) and severe (1.9 [1.3-2.4], P < .001) CSM. DBSI offers granular data on white matter tract integrity in CSM that provide novel insights into disease pathology, supporting its potential utility as a biomarker of CSM disease progression.

INTRODUCTION: Diffusion basis spectrum imaging (DBSI) is a non-invasive quantitative imaging modality that may improve understanding of cervical spondylotic myelopathy (CSM) pathology through detailed evaluations of spinal cord microstructural compartments. METHODS: A single-center prospective cohort study enrolled fifty CSM patients and twenty controls from 2018-2020. All patients underwent clinical evaluation and diffusion-weighted MRI, followed by diffusion tensor imaging (DTI) and DBSI analyses. Diffusion-weighted MRI metrics assessed white matter integrity by fractional anisotropy, axial diffusivity, radial diffusivity, and fiber fraction. In addition, DBSI further evaluates extra-axonal changes by isotropic restricted and non-restricted fraction. Including an intra-axonal diffusion compartment, DBSI improves estimations of axonal injury via intra-axonal axial diffusivity. Patients were categorized into mild, moderate, and severe CSM using mJOA classifications. Imaging parameters were compared among patient groups using independent-samples t-tests and ANOVA. RESULTS: Twenty controls, 27 mild (mJOA 15-17), 12 moderate (12-14) and 11 severe (0-11) CSM patients were enrolled. All patient-reported outcome measures were worse in CSM patients (all p &lt; 0.001). DTI and DBSI fractional anisotropy, axial diffusivity, and radial diffusivity were significantly different between control and CSM patients (p &lt; 0.05). DBSI fiber fraction, restricted fraction, and non-restricted fraction were significantly different between groups (p &lt; 0.01). DBSI intra-axonal axial diffusivity was lower in mild compared to moderate (mean difference [95% CI]: 1.1 [0.3, 2.1], p &lt; 0.01) and severe (1.9 [1.3, 2.4], p &lt; 0.001) CSM. CONCLUSIONS: DBSI offers granular data on white matter tract integrity in CSM that provide novel insights into disease pathology, supporting its potential utility as a biomarker of CSM disease progression.

EVALUATING NEUROIMMUNE IMAGING AS A BIOMARKER OF TISSUE CELLULARITY IN POSTMORTEM HUMAN BRAIN

BackgroundAlzheimer disease (AD) is the most common type of dementia.There is growing evidence that the amyloid plaques in postmortem AD human brains are surrounded by activated microglia. Using diffusion basis spectrum imaging (DBSI), we have previously observed increased cellular diffusivity in AD patients, suggesting increased microglia activation as a key pathology in AD. To better understand the underlying mechanism and further establish the noninvasive and nonradioactive DBSI biomarkers of microglia activation, we conducted a realistic Monte Carlo (MC) simulation to model diffusion MRI signals associated with microglia in various activation states.MethodFirst, realistic microglia diffusion signals were generated using MC simulation with real 3D microglia geometry obtained from neuromorpho.org (Fig. 1A). We simulated different pathophysiological scenarios to validate DBSI’s capability in quantitatively detecting microglia activation (Fig. 1B). Second, we conducted and ex vivo MRI scans on human postmortem AD brain samples, followed by immunohistochemical (IHC) staining of microglia (Iba‐1) in aligned sections from the same tissue. DBSI cell apparent diffusion coefficients (ADC), reflecting microglia activation, were estimated and compared to quantitative histological assessments of microglia activation. Finally, in vivo DBSI was conducted on 200 participants who were classified into healthy control, preclinical AD, and early symptomatic AD groups based on cognitive assessments and measures of CSF amyloid (Aβ42) and pTau181.ResultTwo exemplary regions in grey matter (GM) and white matter (WM) of a postmortem AD brain were selected (Fig. 1C). We found that GM had significantly higher DBSI‐derived cell ADC than WM (Fig. 1D). Iba‐1 IHC revealed that WM had significantly larger average microglial area (p&lt;0.005) and bigger max microglia larea (Fig. 1E‐F). MC Simulation was conducted on 700 microglia models. Microglial activation would result in an increased DBSI cell ADC (Fig. 1G). According to MC simulation, increased DBSI‐derived cell ADC in preclinical and early symptomatic AD indicated microglial activation in preclinical and early symptomatic AD (Fig. 1H).ConclusionDBSI‐derived cell ADC increases with microglial activation as assessed by quantitative Iba‐1 IHC. This finding is supported by MC simulation using real 3D microglia geometry. The study indicates that DBSI has the potential to provide non‐invasive MRI biomarkers of microglia activation.

As diffusion tensor imaging gains widespread use, many researchers have been motivated to go beyond the tensor model and fit more complex diffusion models, to gain a more complete description of white matter microstructure and associated pathology. Two such models are diffusion kurtosis imaging (DKI) and diffusion basis spectrum imaging (DBSI). It is not clear which DKI parameters are most closely related to DBSI parameters, so in the interest of enabling comparisons between DKI and DBSI studies, we conducted an empirical survey of the interrelation of these models in 12 healthy volunteers using the same diffusion acquisition. We found that mean kurtosis is positively associated with the DBSI fiber ratio and negatively associated with the hindered ratio. This was primarily driven by the radial component of kurtosis. The axial component of kurtosis was strongly and specifically correlated with the restricted ratio. The joint spatial distributions of DBSI and DKI parameters are tissue-dependent and stable across healthy individuals. Our contribution is a better understanding of the biological interpretability of the parameters generated by the two models in healthy individuals.

Promising treatments are being developed to promote functional recovery after spinal cord injury (SCI). Magnetic resonance imaging, specifically Diffusion Tensor Imaging (DTI) has been shown to non-invasively measure both axonal and myelin integrity following traumatic brain and SCI. A novel data-driven model-selection algorithm known as Diffusion Basis Spectrum Imaging (DBSI) has been proposed to more accurately delineate white matter injury. The objective of this study was to investigate whether DTI/DBSI changes that extend to level of the cerebral peduncle and internal capsule following a SCI could be correlated with clinical function. A prospective non-randomized cohort of 23 patients with chronic spinal cord injuries and 17 control subjects underwent cranial diffusion weighted imaging, followed by whole brain DTI and DBSI computations. Region-based analyses were performed on cerebral peduncle and internal capsule. Three subgroups of patients were included in the region-based analysis. Tract-Based Spatial Statistics (TBSS) was also applied to allow whole-brain white matter analysis between controls and all patients. Functional assessments were made using International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) as modified by the American Spinal Injury Association (ASIA) Scale. Whole brain white matter analysis using TBSS finds no statistical difference between controls and all patients. Only cervical ASIA A/B patients in cerebral peduncle showed differences from controls in DTI and DBSI results with region-based analysis. Cervical ASIA A/B SCI patients had higher levels of axonal injury and edema/tissue loss as measured by DBSI at the level of the cerebral peduncle. DTI Fractional Anisotropy (FA), Axial Diffusivity (AD) and Radial Diffusivity (RD) was able to detect differences in cervical ASIA A/B patients, but were non-specific to pathologies. Increased water fraction indicated by DBSI non-restricted isotropic diffusion fraction in the cerebral peduncle, explains the simultaneously increased DTI AD and DTI RD values. Our results further demonstrate the utility of DTI to detect disruption in axonal integrity in white matter, yet a clear shortcoming in differentiating true axonal injury from inflammation/tissue loss. Our results suggest a preservation of axonal integrity at the cortical level and has implications for future regenerative clinical trials.

To compare the breathhold, navigator-triggered, and free-breathing techniques in diffusion-weighted magnetic resonance imaging (MRI) for the evaluation of focal liver lesions on a 3.0T system. Fifty-two patients (36 men, 16 women; mean age, 56.4 years) with focal liver lesions underwent breathhold, navigator-triggered, and free-breathing diffusion-weighted imaging (DWI) of the liver on a 3.0 Tesla (T) system. All sequences were performed with b values of 50 and 800 s/mm(2) and identical parameters except for signal averages (two for navigator-triggered, one for breathhold, and four for free-breathing) and repetition time (3389 ms for navigator-triggered, 1500 ms for breathhold, and 4400 ms for free-breathing). A total of 74 lesions (50 malignant, 24 benign) were evaluated. The signal-to-noise ratios (SNR) of the liver and lesions, contrast-to-noise ratios (CNR) of each lesion, and ADC values of the liver and lesions were compared for each DWI sequence. The detection sensitivity and characterization accuracy were also compared. The SNRs of the liver and lesions were significantly lower for breathhold DWI than for non-breathhold DWI (navigator-triggered and free-breathing DWI) for all b values. The CNRs of the lesions were also significantly lower for breathhold DWI than for non-breathhold DWI. The ADC values of the liver and focal lesions measured using the three DWI techniques were not significantly different and showed good correlation. For lesion detection and characterization, there were no significant differences between breathhold and non-breathhold DWI. Both breathhold and non-breathhold DWI are comparable for the detection or characterization of focal liver lesions at 3.0T; however, non-breathhold DWI provides higher SNR and CNR than breathhold DWI. In addition, although free-breathing and navigator-triggered DWI sequences show similar performance for 3.0T liver imaging, free-breathing DWI is more time efficient than navigator-triggered DWI.

Microstructural abnormalities of the right hemisphere in preschool autism spectrum disorders

Diffusion basis spectrum imaging (DBSI) models diffusion-weighted magnetic resonance imaging (MRI) signals as a combination of discrete anisotropic diffusion tensors and a spectrum of isotropic diffusion tensors. Here, we report the histopathological correlates of DBSI in the biopsied brain tissue of a patient with an inflammatory demyelinating lesion typical of multiple sclerosis (MS). Increased radial diffusivity (marker of demyelination), decreased fiber fraction (apparent axonal density), elevated nonrestricted isotropic fraction (marker of vasogenic edema), but unchanged axial diffusivity (marker of integrity of residual axons) seen in the lesion appeared consistent with histopathological findings of inflammatory demyelination with relative axonal sparing. Our report supports the application of DBSI as a biomarker in human studies of MS.

Diffusion-weighted echo-planar imaging of the head and neck using 3-T MRI: Investigation into the usefulness of liquid perfluorocarbon pads and choice of optimal fat suppression method

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