Deterministic Diffusion Fiber Tracking Improved by Quantitative Anisotropy

Sun

et al. 2015

Brain

139

189

Axon injury/loss, demyelination and inflammation are the primary pathologies in multiple sclerosis lesions. Despite the prevailing notion that axon/neuron loss is the substrate of clinical progression of multiple sclerosis, the roles that these individual pathological processes play in multiple sclerosis progression remain to be defined. An imaging modality capable to effectively detect, differentiate and individually quantify axon injury/loss, demyelination and inflammation, would not only facilitate the understanding of the pathophysiology underlying multiple sclerosis progression, but also the assessment of treatments at the clinical trial and individual patient levels. In this report, the newly developed diffusion basis spectrum imaging was used to discriminate and quantify the underlying pathological components in multiple sclerosis white matter. Through the multiple-tensor modelling of diffusion weighted magnetic resonance imaging signals, diffusion basis spectrum imaging resolves inflammation-associated cellularity and vasogenic oedema in addition to accounting for partial volume effects resulting from cerebrospinal fluid contamination, and crossing fibres. Quantitative histological analysis of autopsied multiple sclerosis spinal cord specimens supported that diffusion basis spectrum imaging-determined cellularity, axon and myelin injury metrics closely correlated with those pathologies identified and quantified by conventional histological staining. We demonstrated in healthy control subjects that diffusion basis spectrum imaging rectified inaccurate assessments of diffusion properties of white matter tracts by diffusion tensor imaging in the presence of cerebrospinal fluid contamination and/or crossing fibres. In multiple sclerosis patients, we report that diffusion basis spectrum imaging quantitatively characterized the distinct pathologies underlying gadolinium-enhanced lesions, persistent black holes, non-enhanced lesions and non-black hole lesions, a task yet to be demonstrated by other neuroimaging approaches. Diffusion basis spectrum imaging-derived radial diffusivity (myelin integrity marker) and non-restricted isotropic diffusion fraction (oedema marker) correlated with magnetization transfer ratio, supporting previous reports that magnetization transfer ratio is sensitive not only to myelin integrity, but also to inflammation-associated oedema. Our results suggested that diffusion basis spectrum imaging-derived quantitative biomarkers are highly consistent with histology findings and hold promise to accurately characterize the heterogeneous white matter pathology in multiple sclerosis patients. Thus, diffusion basis spectrum imaging can potentially serve as a non-invasive outcome measure to assess treatment effects on the specific components of underlying pathology targeted by new multiple sclerosis therapies. Keywords: diffusion basis spectrum imaging; diffusion tensor imaging; white matter injury; inflammation; multiple sclerosis Abbreviations: DTI = diffusion tensor imaging; DBSI = diffusion...

Section: Dbsi Tractographymentioning

confidence: 99%

Differentiation and quantification of inflammation, demyelination and axon injury or loss in multiple sclerosis

Sun

et al. 2015

Brain

139

189

“…48 A whole brain seeding approach using multiple, single-slice ROI and region of avoidance masks was implemented. For CST reconstruction, 2 ROIs were drawn in the axial plane to cover the white matter of the medulla and the posterior limb of the internal capsule just superior to the midbrain in each hemisphere.…”

Section: Fiber Trackingmentioning

confidence: 99%

“…Accurate depiction of the perilesional CST including in the edematous zone using HDFT is linked in part to the QA being less sensitive to partial volume effects. 3,48 The surgical planning in our studies 1,15,16 for mass lesions has been based on the principle of avoidance of damage to the displaced tracts as a result of the initial surgical trajectory or eventual lesionectomy. This is related to the hypothesis that displaced tracts, even though functionally compromised, retain the ability to recover after removal of the mass effect, leading to resolution of the associated neurological deficits over time, as demonstrated here.…”

Section: Tractography-based Qualitative Data and Implicationsmentioning

confidence: 99%

“…16 HDFT relies on diffusion spectrum imaging (DSI) for acquisition, 44 generalized q-sampling imaging for fiber orientation estimation, and a generalized deterministic fiber tracking method. 48 We have reported its use in studies on several white matter tracts 18,19,[41][42][43] and in a study concerning its utility for surgical planning for space-occupying lesions. 16 Of direct relevance to this report, the utility of HDFT was recently reported in characterizing changes in the perilesional white matter and in guiding surgical planning in patients with supratentorial CMs using a combined qualitative and quantitative approach.…”

mentioning

confidence: 99%

“…1 QA overcomes the limitations of FA in assessing the fiber integrity in areas with multiple crossing fibers since QA is less sensitive to partial volume effects, as demonstrated in our recent study. 48 The resistance of QA to multiple crossing fibers also enabled us to aim to indirectly ascertain the craniocaudal integrity of the affected CST by obtaining quantitative information with respect to 3 rostrocaudal segments (perilesional and proximal and distal to the lesion). We longitudinally monitored the qualitative and quantitative tractography data, aiming to indirectly assess the craniocaudal integrity of an affected tract over time.…”

mentioning

confidence: 99%

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Longitudinal evaluation of corticospinal tract in patients with resected brainstem cavernous malformations using high-definition fiber tractography and diffusion connectometry analysis: preliminary experience

Faraji¹,

Kumar²,

Jarbo

et al. 2015

JNS

Self Cite

abbreviatioNs ADL = activities of daily living; CC = corpus callosum; CM = cavernous malformation; CN = cranial nerve; CST = corticospinal tract; DSI = diffusion spectrum imaging; DTI = diffusion tensor imaging; FDR = false discovery rate; HDFT = high-definition fiber tractography; ICH = intracerebral hemorrhage; QA = quantitative anisotropy; ROI = region of interest; SRS = stereotactic radiosurgery. obJect Brainstem cavernous malformations (CMs) are challenging due to a higher symptomatic hemorrhage rate and potential morbidity associated with their resection. The authors aimed to preoperatively define the relationship of CMs to the perilesional corticospinal tracts (CSTs) by obtaining qualitative and quantitative data using high-definition fiber tractography. These data were examined postoperatively by using longitudinal scans and in relation to patients' symptomatology. The extent of involvement of the CST was further evaluated longitudinally using the automated "diffusion connectometry" analysis. methods Fiber tractography was performed with DSI Studio using a quantitative anisotropy (QA)-based generalized deterministic tracking algorithm. Qualitatively, CST was classified as being "disrupted" and/or "displaced." Quantitative analysis involved obtaining mean QA values for the CST and its perilesional and nonperilesional segments. The contralateral CST was used for comparison. Diffusion connectometry analysis included comparison of patients' data with a template from 90 normal subjects. results Three patients (mean age 22 years) with symptomatic pontomesencephalic hemorrhagic CMs and varying degrees of hemiparesis were identified. The mean follow-up period was 37.3 months. Qualitatively, CST was partially disrupted and displaced in all. Direction of the displacement was different in each case and progressively improved corresponding with the patient's neurological status. No patient experienced neurological decline related to the resection. The perilesional mean QA percentage decreases supported tract disruption and decreased further over the follow-up period (Case 1, 26%-49%; Case 2, 35%-66%; and Case 3, 63%-78%). Diffusion connectometry demonstrated rostrocaudal involvement of the CST consistent with the quantitative data. coNclusioNs Hemorrhagic brainstem CMs can disrupt and displace perilesional white matter tracts with the latter occurring in unpredictable directions. This requires the use of tractography to accurately define their orientation to optimize surgical entry point, minimize morbidity, and enhance neurological outcomes. Observed anisotropy decreases in the perilesional segments are consistent with neural injury following hemorrhagic insults. A model using these values in different CST segments can be used to longitudinally monitor its craniocaudal integrity. Diffusion connectometry is a complementary approach providing longitudinal information on the rostrocaudal involvement of the CST.

Comparison of Functional and Structural Neural Network Features in Older Adults With Depression With vs Without Apathy and Association With Response to Escitalopram

et al. 2022

IMPORTANCEApathy is prevalent among individuals with late-life depression and is associated with poor response to pharmacotherapy, including chronicity and disability. Elucidating brain networks associated with apathy and poor treatment outcomes can inform intervention development. OBJECTIVES To assess the brain network features of apathy among individuals with late-life depression and identify brain network abnormalities associated with poor antidepressant response. DESIGN, SETTING, AND PARTICIPANTS This secondary analysis of a single-group, open-label nonrandomized clinical trial of escitalopram conducted at an outpatient geriatric psychiatry clinic enrolled 40 adults aged 59 to 85 years with major depressive disorder from July 1, 2012, to July 31, 2019. INTERVENTIONS After a 2-week washout period, participants received escitalopram titrated to a target of 20 mg/d for 12 weeks. MAIN OUTCOMES AND MEASURES Baseline and posttreatment magnetic resonance imaging (MRI), clinical, and cognitive assessments were conducted. Functional MRI was used to map group differences in resting state functional connectivity (rsFC) of the salience network, and diffusion MRI connectometry was performed to evaluate pathway-level disruptions in structural connectivity. The Apathy Evaluation Scale was used to quantify apathy, and the Hamilton Depression Rating Scale (HAM-D) was used to quantify the primary outcome of depression severity. RESULTS Forty participants (26 women [65%]; mean [SD] age, 70.0 [6.6] years [range, 59-85 years]) with depression were included; 20 participants (50%) also had apathy. Relative to nonapathetic participants with depression, those with depression and apathy had lower rsFC of salience network seeds with the dorsolateral prefrontal cortex (DLPFC), premotor cortex, midcingulate cortex, and paracentral lobule and greater rsFC with the lateral temporal cortex and temporal pole (z score >2.7; Bonferroni-corrected threshold of P < .0125). Compared with participants without apathy, those with apathy had lower structural connectivity in the splenium, cingulum, and fronto-occipital fasciculus (t score >2.5; false discovery rate-corrected P = .02). Twenty-seven participants completed escitalopram treatment; 16 (59%) achieved remission (HAM-D score <10). Lower insula-DLPFC/midcingulate cortex rsFC was associated with less symptomatic improvement (HAM-D % change) (β [df] = 0.588 [26]; P = .001) and a higher likelihood of nonremission (odds ratio, 1.041 [95% CI, 1.003-1.081]; P = .04) after treatment and, in regression models, was a mediator of the association between baseline apathy and persistence of depression.(continued) Key Points Question What are the brain network features of apathy in late-life depression, and how are they associated with treatment outcomes? Findings In this secondary analysis of a 12-week nonrandomized single-group trial of escitalopram titrated to 20 mg/d, compared with 20 older adults with depression without apathy, 20 older adults with depression and apathy showed distinct alterations in ne...