Altered integrity of corpus callosum in generalized epilepsy in relation to seizure lateralization after corpus callosotomy.

OBJECTIVE: Generalized-onset seizures are usually conceptualized as engaging bilaterally distributed networks with no clear focus. However, the authors previously reported a case series demonstrating that in some patients with generalized-onset seizures, focal seizure onset could be discovered after corpus callosotomy. The corpus callosum is considered to be a major pathway for seizure generalization in this group of patients. The authors hypothesized that, in patients with generalized-onset seizures, the structure of the corpus callosum could be different between patients who have lateralized seizures and those who have nonlateralized seizures after corpus callosotomy. The authors aimed to evaluate the structural difference through statistical analysis of diffusion tensor imaging (DTI) scalars between these two groups of patients. METHODS: Thirty-two patients diagnosed with generalized-onset motor seizures and without an MRI lesion were included in this study. Among them, 16 patients developed lateralized epileptic activities after corpus callosotomy, and the remaining 16 patients continued to have nonlateralized seizures after corpus callosotomy. Presurgical DTI studies were acquired to quantify the structural integrity of the corpus callosum. RESULTS: The DTI analysis showed significant reduction of fractional anisotropy (FA) and increase in radial diffusivity (RD) in the body of the corpus callosum in the lateralized group compared with the nonlateralized group. CONCLUSIONS: The authors' findings indicate the existence of different configurations of bilateral epileptic networks in generalized epilepsy. Generalized seizures with focal onset relying on rapid spread through the corpus callosum might cause more structural damage related to demyelination in the corpus callosum, showing reduced FA and increased RD. This study suggests that presurgical DTI analysis of the corpus callosum might predict the seizure lateralization after corpus callosotomy.

Diffusion tensor magnetic resonance imaging of the optic nerves in pediatric hydrocephalus.

OBJECTIVE: While conventional imaging can readily identify ventricular enlargement in hydrocephalus, structural changes that underlie microscopic tissue injury might be more difficult to capture. MRI-based diffusion tensor imaging (DTI) uses properties of water motion to uncover changes in the tissue microenvironment. The authors hypothesized that DTI can identify alterations in optic nerve microstructure in children with hydrocephalus. METHODS: The authors retrospectively reviewed 21 children (< 18 years old) who underwent DTI before and after neurosurgical intervention for acute obstructive hydrocephalus from posterior fossa tumors. Their optic nerve quantitative DTI metrics of mean diffusivity (MD) and fractional anisotropy (FA) were compared to those of 21 age-matched healthy controls. RESULTS: Patients with hydrocephalus had increased MD and decreased FA in bilateral optic nerves, compared to controls (p < 0.001). Normalization of bilateral optic nerve MD and FA on short-term follow-up (median 1 day) after neurosurgical intervention was observed, as was near-complete recovery of MD on long-term follow-up (median 1.8 years). CONCLUSIONS: DTI was used to demonstrate reversible alterations of optic nerve microstructure in children presenting acutely with obstructive hydrocephalus. Alterations in optic nerve MD and FA returned to near-normal levels on short- and long-term follow-up, suggesting that surgical intervention can restore optic nerve tissue microstructure. This technique is a safe, noninvasive imaging tool that quantifies alterations of neural tissue, with a potential role for evaluation of pediatric hydrocephalus.

The role of diffusion tensor imaging in the diagnosis, prognosis, and assessment of recovery and treatment of spinal cord injury: a systematic review.

OBJECTIVEDiffusion tensor imaging (DTI) is an MRI tool that provides an objective, noninvasive, in vivo assessment of spinal cord injury (SCI). DTI is significantly better at visualizing microstructures than standard MRI sequences. In this imaging modality, the direction and amplitude of the diffusion of water molecules inside tissues is measured, and this diffusion can be measured using a variety of parameters. As a result, the potential clinical application of DTI has been studied in several spinal cord pathologies, including SCI. The aim of this study was to describe the current state of the potential clinical utility of DTI in patients with SCI and the challenges to its use as a tool in clinical practice.METHODSA search in the PubMed database was conducted for articles relating to the use of DTI in SCI. The citations of relevant articles were also searched for additional articles.RESULTSAmong the most common DTI metrics are fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. Changes in these metrics reflect changes in tissue integrity. Several DTI metrics and combinations thereof have demonstrated significant correlations with clinical function both in model species and in humans. Its applications encompass the full spectrum of the clinical assessment of SCI including diagnosis, prognosis, recovery, and efficacy of treatments in both the spinal cord and potentially the brain.CONCLUSIONSDTI and its metrics have great potential to become a powerful clinical tool in SCI. However, the current limitations of DTI preclude its use beyond research and into clinical practice. Further studies are needed to significantly improve and resolve these limitations as well as to determine reliable time-specific changes in multiple DTI metrics for this tool to be used accurately and reliably in the clinical setting.

The role of diffusion tensor imaging and fractional anisotropy in the evaluation of patients with idiopathic normal pressure hydrocephalus: a literature review.

OBJECTIVE Diffusion tensor imaging (DTI) for the assessment of fractional anisotropy (FA) and involving measurements of mean diffusivity (MD) and apparent diffusion coefficient (ADC) represents a novel, MRI-based, noninvasive technique that may delineate microstructural changes in cerebral white matter (WM). For example, DTI may be used for the diagnosis and differentiation of idiopathic normal pressure hydrocephalus (iNPH) from other neurodegenerative diseases with similar imaging findings and clinical symptoms and signs. The goal of the current study was to identify and analyze recently published series on the use of DTI as a diagnostic tool. Moreover, the authors also explored the utility of DTI in identifying patients with iNPH who could be managed by surgical intervention. METHODS The authors performed a literature search of the PubMed database by using any possible combinations of the following terms: "Alzheimer's disease," "brain," "cerebrospinal fluid," "CSF," "diffusion tensor imaging," "DTI," "hydrocephalus," "idiopathic," "magnetic resonance imaging," "normal pressure," "Parkinson's disease," and "shunting." Moreover, all reference lists from the retrieved articles were reviewed to identify any additional pertinent articles. RESULTS The literature search retrieved 19 studies in which DTI was used for the identification and differentiation of iNPH from other neurodegenerative diseases. The DTI protocols involved different approaches, such as region of interest (ROI) methods, tract-based spatial statistics, voxel-based analysis, and delta-ADC analysis. The most studied anatomical regions were the periventricular WM areas, such as the internal capsule (IC), the corticospinal tract (CST), and the corpus callosum (CC). Patients with iNPH had significantly higher MD in the periventricular WM areas of the CST and the CC than had healthy controls. In addition, FA and ADCs were significantly higher in the CST of iNPH patients than in any other patients with other neurodegenerative diseases. Gait abnormalities of iNPH patients were statistically significantly and negatively correlated with FA in the CST and the minor forceps. Fractional anisotropy had a sensitivity of 94% and a specificity of 80% for diagnosing iNPH. Furthermore, FA and MD values in the CST, the IC, the anterior thalamic region, the fornix, and the hippocampus regions could help differentiate iNPH from Alzheimer or Parkinson disease. Interestingly, CSF drainage or ventriculoperitoneal shunting significantly modified FA and ADCs in iNPH patients whose condition clinically responded to these maneuvers. CONCLUSIONS Measurements of FA and MD significantly contribute to the detection of axonal loss and gliosis in the periventricular WM areas in patients with iNPH. Diffusion tensor imaging may also represent a valuable noninvasive method for differentiating iNPH from other neurodegenerative diseases. Moreover, DTI can detect dynamic changes in the WM tracts after lumbar drainage or shunting procedures and could help identify iNPH patients who may benefit from surgical intervention.

4.7-T diffusion tensor imaging of acute traumatic peripheral nerve injury.

Diagnosis and management of peripheral nerve injury is complicated by the inability to assess microstructural features of injured nerve fibers via clinical examination and electrophysiology. Diffusion tensor imaging (DTI) has been shown to accurately detect nerve injury and regeneration in crush models of peripheral nerve injury, but no prior studies have been conducted on nerve transection, a surgical emergency that can lead to permanent weakness or paralysis. Acute sciatic nerve injuries were performed microsurgically to produce multiple grades of nerve transection in rats that were harvested 1 hour after surgery. High-resolution diffusion tensor images from ex vivo sciatic nerves were obtained using diffusion-weighted spin-echo acquisitions at 4.7 T. Fractional anisotropy was significantly reduced at the injury sites of transected rats compared with sham rats. Additionally, minor eigenvalues and radial diffusivity were profoundly elevated at all injury sites and were negatively correlated to the degree of injury. Diffusion tensor tractography showed discontinuities at all injury sites and significantly reduced continuous tract counts. These findings demonstrate that high-resolution DTI is a promising tool for acute diagnosis and grading of traumatic peripheral nerve injuries.

Diffusion tensor imaging in cervical spondylotic myelopathy: a review.

Degenerative spondylotic myelopathy is the most common cause of spinal dysfunction, as well as nontraumatic spastic paraparesis and quadriparesis. Although conventional MRI is the gold standard for radiographic evaluation of the spinal cord, it has limited application for determining prognosis and recovery. In the last decade, diffusion tensor imaging (DTI), which is based on the property of preferential diffusion of water molecules, has gained popularity in evaluating patients with cervical spondylotic myelopathy (CSM). The use of DTI allows for evaluation of microstructural changes in the spinal cord not otherwise detected on routine conventional MRI. In this review, the authors describe the application of DTI in CSM evaluation and its role as an imaging biomarker to predict disease severity and prognosis.

Feasibility of fast brain diffusion MRI to quantify white matter injury in pediatric hydrocephalus.

OBJECTIVE: Traditionally, diffusion MRI (dMRI) has been performed in parallel with high-resolution conventional MRI, which requires long scan times and may require sedation or general anesthesia in infants and young children. Conversely, fast brain MRI permits image acquisition without the need for sedation, although its short pulse sequences, susceptibility to motion artifact, and contrast resolution have limited its use to assessing ventricular size or major structural variations. Here, the authors demonstrate the feasibility of leveraging a 3-direction fast brain MRI protocol to obtain reliable dMRI measures. METHODS: Fast brain MRI with 3-direction dMRI was performed in infants and children before and after hydrocephalus treatment. Regions of interest in the posterior limbs of the internal capsules (PLICs) and the genu of the corpus callosum (gCC) were drawn on diffusion-weighted images, and mean diffusivity (MD) data were extracted. Ventricular size was determined by the frontal occipital horn ratio (FOHR). Differences between and within groups pre- and posttreatment, and FOHR-MD correlations were assessed. RESULTS: Of 40 patients who met inclusion criteria (median age 27.5 months), 15 (37.5%), 17 (42.5%), and 8 (20.0%) had posthemorrhagic hydrocephalus (PHH), congenital hydrocephalus (CH), or no intracranial abnormality (controls), respectively. A hydrocephalus group included both PHH and CH patients. Prior to treatment, the FOHR (p < 0.001) and PLIC MD (p = 0.027) were greater in the hydrocephalus group than in the controls. While the mean gCC MD in the hydrocephalus group (1.10 × 10-3 mm2/sec) was higher than that of the control group (0.98), the difference was not significant (p = 0.135). Following a median follow-up duration of 14 months, decreases in FOHR, PLIC MD, and gCC MD were observed in the hydrocephalus group and were similar to those in the control group (p = 0.107, p = 0.702, and p = 0.169, respectively). There were no correlations identified between FOHR and MDs at either time point. CONCLUSIONS: The utility of fast brain MRI can be extended beyond anatomical assessments to obtain dMRI measures. A reduction in PLIC and gCC MD to levels similar to those of controls was observed within 14 months following shunt surgery for hydrocephalus in PHH and CH infants. Further studies are required to assess the role of fast brain dMRI for assessing clinical outcomes in pediatric hydrocephalus patients.

First application of 7-T ultra-high field diffusion tensor imaging to detect altered microstructure of thalamic-somatosensory anatomy in trigeminal neuralgia.

OBJECTIVE: Trigeminal neuralgia (TN) is a debilitating neurological disease that commonly results from neurovascular compression of the trigeminal nerve (CN V). Although the CN V has been extensively studied at the site of neurovascular compression, many pathophysiological factors remain obscure. For example, thalamic-somatosensory function is thought to be altered in TN, but the abnormalities are inadequately characterized. Furthermore, there are few studies using 7-T MRI to examine patients with TN. The purpose of the present study was to use 7-T MRI to assess microstructural alteration in the thalamic-somatosensory tracts of patients with TN by using ultra-high field MRI. METHODS: Ten patients with TN and 10 age- and sex-matched healthy controls underwent scanning using 7-T MRI with diffusion tensor imaging. Structural images were segmented with an automated algorithm to obtain thalamus and primary somatosensory cortex (S1). Probabilistic tractography was performed between the thalamus and S1, and the microstructure of the thalamic-somatosensory tracts was compared between patients with TN and controls. RESULTS: Fractional anisotropy of the thalamic-somatosensory tract ipsilateral to the site of neurovascular compression was reduced in patients (mean 0.43) compared with side-matched controls (mean 0.47, p = 0.01). The mean diffusivity was increased ipsilaterally in patients (mean 6.58 × 10-4 mm2/second) compared with controls (mean 6.15 × 10-4 mm2/second, p = 0.02). Radial diffusivity was increased ipsilaterally in patients (mean 4.91 × 10-4 mm2/second) compared with controls (mean 4.44 × 10-4 mm2/second, p = 0.01). Topographical analysis revealed fractional anisotropy reduction and diffusivity elevation along the entire anatomical S1 arc in patients with TN. CONCLUSIONS: The present study is the first to examine microstructural properties of the thalamic-somatosensory anatomy in patients with TN and to evaluate quantitative differences compared with healthy controls. The finding of reduced integrity of these white matter fibers provides evidence of microstructural alteration at the level of the thalamus and S1, and furthers the understanding of TN neurobiology.

Stereotactic laser ablation for completion corpus callosotomy.

OBJECTIVE: Completion corpus callosotomy can offer further remission from disabling seizures when a prior partial corpus callosotomy has failed and residual callosal tissue is identified on imaging. Traditional microsurgical approaches to section residual fibers carry risks associated with multiple craniotomies and the proximity to the medially oriented motor cortices. Laser interstitial thermal therapy (LITT) represents a minimally invasive approach for the ablation of residual fibers following a prior partial corpus callosotomy. Here, the authors report clinical outcomes of 6 patients undergoing LITT for completion corpus callosotomy and characterize the radiological effects of ablation. METHODS: A retrospective clinical review was performed on a series of 6 patients who underwent LITT completion corpus callosotomy for medically intractable epilepsy at Stanford University Medical Center and Lucile Packard Children's Hospital at Stanford between January 2015 and January 2018. Detailed structural and diffusion-weighted MR images were obtained prior to and at multiple time points after LITT. In 4 patients who underwent diffusion tensor imaging (DTI), streamline tractography was used to reconstruct and evaluate tract projections crossing the anterior (genu and rostrum) and posterior (splenium) parts of the corpus callosum. Multiple diffusion parameters were evaluated at baseline and at each follow-up. RESULTS: Three pediatric (age 8-18 years) and 3 adult patients (age 30-40 years) who underwent completion corpus callosotomy by LITT were identified. Mean length of follow-up postoperatively was 21.2 (range 12-34) months. Two patients had residual splenium, rostrum, and genu of the corpus callosum, while 4 patients had residual splenium only. Postoperative complications included asymptomatic extension of ablation into the left thalamus and transient disconnection syndrome. Ablation of the targeted area was confirmed on immediate postoperative diffusion-weighted MRI in all patients. Engel class I-II outcomes were achieved in 3 adult patients, whereas all 3 pediatric patients had Engel class III-IV outcomes. Tractography in 2 adult and 2 pediatric patients revealed time-dependent reduction of fractional anisotropy after LITT. CONCLUSIONS: LITT is a safe, minimally invasive approach for completion corpus callosotomy. Engel outcomes for completion corpus callosotomy by LITT were similar to reported outcomes of open completion callosotomy, with seizure reduction primarily observed in adult patients. Serial DTI can be used to assess the presence of tract projections over time but does not classify treatment responders or nonresponders.

Posterior fossa syndrome and increased mean diffusivity in the olivary bodies.

OBJECTIVE: Posterior fossa syndrome (PFS) is a common postoperative complication following resection of posterior fossa tumors in children. It typically presents 1 to 2 days after surgery with mutism, ataxia, emotional lability, and other behavioral symptoms. Recent structural MRI studies have found an association between PFS and hypertrophic olivary degeneration, which is detectable as T2 hyperintensity in the inferior olivary nuclei (IONs) months after surgery. In this study, the authors investigated whether immediate postoperative diffusion tensor imaging (DTI) of the ION can serve as an early imaging marker of PFS. METHODS: The authors retrospectively reviewed pediatric brain tumor patients treated at their institution, Lucile Packard Children's Hospital at Stanford, from 2004 to 2016. They compared the immediate postoperative DTI studies obtained in 6 medulloblastoma patients who developed PFS to those of 6 age-matched controls. RESULTS: Patients with PFS had statistically significant increased mean diffusivity (MD) in the left ION (1085.17 ± 215.51 vs 860.17 ± 102.64, p = 0.044) and variably increased MD in the right ION (923.17 ± 119.2 vs 873.67 ± 60.16, p = 0.385) compared with age-matched controls. Patients with PFS had downward trending fractional anisotropy (FA) in both the left (0.28 ± 0.06 vs 0.23 ± 0.03, p = 0.085) and right (0.29 ± 0.06 vs 0.25 ± 0.02, p = 0.164) IONs compared with age-matched controls, although neither of these values reached statistical significance. CONCLUSIONS: Increased MD in the ION is associated with development of PFS. ION MD changes may represent an early imaging marker of PFS.

Quantitative assessment of secondary white matter injury in the visual pathway by pituitary adenomas: a multimodal study at 7-Tesla MRI.

OBJECTIVE: The objective of this study was to investigate microstructural damage caused by pituitary macroadenomas by performing probabilistic tractography of the optic tracts and radiations using 7-T diffusion-weighted MRI (DWI). These imaging findings were correlated with neuro-ophthalmological results to assess the utility of ultra-high-field MRI for objective evaluation of damage to the anterior and posterior visual pathways. METHODS: Probabilistic tractography employing 7-T DWI was used to reconstruct the optic tracts and radiations in 18 patients with adenomas and in 16 healthy volunteers. Optic chiasm compression was found in 66.7% of the patients and visual defects in 61.1%. Diffusion indices were calculated along the projections and correlated with tumor volumes and results from neuro-ophthalmological examinations. Primary visual cortical thicknesses were also assessed. RESULTS: Fractional anisotropy was reduced by 21.9% in the optic tracts (p < 0.001) and 17.7% in the optic radiations (p < 0.001) in patients with adenomas. Patients showed an 8.5% increase in mean diffusivity of optic radiations compared with healthy controls (p < 0.001). Primary visual cortical thickness was reduced in adenoma patients. Diffusion indices of the visual pathway showed significant correlations with neuro-ophthalmological examination findings. CONCLUSIONS: Imaging-based quantification of secondary neuronal damage from adenomas strongly correlated with neuro-ophthalmological findings. Diffusion characteristics enabled by ultra-high-field DWI may allow preoperative characterization of visual pathway damage in patients with chiasmatic compression and may inform prognosis for vision recoverability.

Reproducibility, temporal stability, and functional correlation of diffusion MR measurements within the spinal cord in patients with asymptomatic cervical stenosis or cervical myelopathy.

OBJECTIVE The purpose of this study was to quantify the reproducibility, temporal stability, and functional correlation of diffusion MR characteristics in the spinal cord in patients with cervical stenosis with or without myelopathy. The association between longitudinal diffusion tensor imaging (DTI) measurements and serial neurological function assessment was explored at both the group and individual level. METHODS Sixty-six nonoperatively treated patients with cervical stenosis were prospectively followed (3 months to > 5 years) using synchronous serial MRI and functional outcome assessment. A total of 183 separate MRI examinations were performed, separated by at least 3 months, and each patient had a minimum of 2 MRI scans (range 2-5 scans). Anatomical and DTI measurements were performed within the spinal cord at the C1-2 region as well as at the area of highest compression. Coefficients of variance (COVs) were compared across measurements in both reference tissue and areas of compression for anatomical measurements, fractional anisotropy (FA), and mean diffusivity (MD). The correlation between diffusion MR measures at the site of compression and evaluations of neurological function assessed using the modified Japanese Orthopaedic Association (mJOA) scale at multiple time points was evaluated. RESULTS The COVs for anatomical measurements (Torg ratio and canal diameter) were between 7% and 10%. The median COV for FA measurements at the site of compression was 9%, and for reference tissue at C1-2 it was 6%. The median COV for MD at the site of compression was approximately 12%, and for reference tissue at C1-2 it was 10%. The FA and MD measurements of C1-2 averaged 0.61 and 0.91 µm2/msec, respectively, whereas the FA and MD measurements at the site of compression averaged 0.51 and 1.26 µm2/msec, respectively. Both FA (slope = 0.037; R2 = 0.3281, p < 0.0001) and MD (slope = -0.074; R2 = 0.1101, p = 0.0084) were significantly correlated with the mJOA score. The FA decreased by approximately 0.032 units per mJOA unit decrease (R2 = 0.2037, p < 0.0001), whereas the MD was increased by approximately 0.084 µm2/msec for every mJOA unit decrease (R2 = 0.1016, p < 0.0001). CONCLUSIONS Quantitative DTI measurements of the spinal cord in patients with cervical stenosis with or without myelopathy have a median COV of 5%-10%, similar to anatomical measurements. The reproducibility of these measurements and significant correlation with functional outcome status suggest a potential role in the evaluation and longitudinal surveillance of nonoperatively treated patients. With respect to the specific DTI measurements, FA within the spinal cord appears slightly more sensitive to neurological function and more stable than measures of MD. Therefore, DTI of the spinal cord may be a clinically feasible imaging technique for longitudinally monitoring patients with cervical spondylotic myelopathy.

Early postsurgical diffusivity metrics for prognostication of long-term pain relief after Gamma Knife radiosurgery for trigeminal neuralgia.

OBJECTIVE: Gamma Knife radiosurgery (GKRS) is an important treatment modality for trigeminal neuralgia (TN). Current longitudinal assessment after GKRS relies primarily on clinical diagnostic measures, which are highly limited in the prediction of long-term clinical benefit. An objective, noninvasive, predictive tool would be of great utility to advance the clinical management of patients. Using diffusion tensor imaging (DTI), the authors' aim was to determine whether early (6 months post-GKRS) target diffusivity metrics can be used to prognosticate long-term pain relief in patients with TN. METHODS: Thirty-seven patients with TN treated with GKRS underwent 3T MRI scans at 6 months posttreatment. Diffusivity metrics of fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity were extracted bilaterally from the radiosurgical target of the affected trigeminal nerve and its contralateral, unaffected nerve. Early (6 months post-GKRS) diffusivity metrics were compared with long-term clinical outcome. Patients were identified as long-term responders if they achieved at least 75% reduction in preoperative pain for 12 months or longer following GKRS. RESULTS: Trigeminal nerve diffusivity at 6 months post-GKRS was predictive of long-term clinical effectiveness, where long-term responders (n = 19) showed significantly lower fractional anisotropy at the radiosurgical target of their affected nerve compared to their contralateral, unaffected nerve and to nonresponders. Radial diffusivity and mean diffusivity, correlates of myelin alterations and inflammation, were also significantly higher in the affected nerve of long-term responders compared to their unaffected nerve. Nonresponders (n = 18) did not exhibit any characteristic diffusivity changes after GKRS. CONCLUSIONS: The authors demonstrate that early postsurgical target diffusivity metrics have a translational, clinical value and permit prediction of long-term pain relief in patients with TN treated with GKRS. Importantly, an association was found between the footprint of radiation and clinical effectiveness, where a sufficient level of microstructural change at the radiosurgical target is necessary for long-lasting pain relief. DTI can provide prognostic information that supplements clinical measures, and thus may better guide the postoperative assessment and clinical decision-making for patients with TN.

Changes in language white matter tract microarchitecture associated with cognitive deficits in patients with presumed low-grade glioma.

OBJECTIVEThe authors conducted a study to determine whether cognitive functioning of patients with presumed low-grade glioma is associated with white matter (WM) tract changes.METHODSThe authors included 77 patients with presumed low-grade glioma who underwent awake surgery between 2005 and 2013. Diffusion tensor imaging with deterministic tractography was performed preoperatively to identify the arcuate, inferior frontooccipital, and uncinate fasciculi and to obtain the mean fractional anisotropy (FA) and mean diffusivity per tract. All patients were evaluated preoperatively using an extensive neuropsychological protocol that included assessments of the language, memory, and attention/executive function domains. Linear regression models were used to analyze each cognitive domain and each diffusion tensor imaging metric of the 3 WM tracts.RESULTSSignificant correlations (corrected for multiple testing) were found between FA of the arcuate fasciculus and results of the repetition test for the language domain (ß = 0.59, p < 0.0001) and between FA of the inferior frontooccipital fasciculus and results of the imprinting test for the memory domain (ß = -0.55, p = 0.002) and the attention test for the attention and executive function domain (ß = -0.62, p = 0.006).CONCLUSIONSIn patients with glioma, language deficits in repetition of speech, imprinting, and attention deficits are associated with changes in the microarchitecture of the arcuate and inferior frontooccipital fasciculi.

Diffusion tensor imaging and ventricle volume quantification in patients with chronic shunt-treated hydrocephalus: a matched case-control study.

OBJECTIVEThe object of this study was to use diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS) to characterize the long-term effects of hydrocephalus and shunting on white matter integrity and to investigate the relationship of ventricular size and alterations in white matter integrity with headache and quality-of-life outcome measures.METHODSPatients with shunt-treated hydrocephalus and age- and sex-matched healthy controls were recruited into the study and underwent anatomical and DTI imaging on a 3-T MRI scanner. All patients were clinically stable, had undergone CSF shunt placement before 2 years of age, and had a documented history of complaints of headaches. Outcome was scored based on the Headache Disability Inventory and the Hydrocephalus Outcome Questionnaire. Fractional anisotropy (FA) and other DTI-based measures (axial, radial, and mean diffusivity; AD, RD, and MD, respectively) were extracted in the corpus callosum and internal capsule with manual region-of-interest delineation and in other regions with TBSS. Paired t-tests, corrected with a 5% false discovery rate, were used to identify regions with significant differences between patients and controls. Within the patient group, linear regression models were used to investigate the relationship between FA or ventricular volume and outcome, as well as the effect of shunt-related covariates.RESULTSTwenty-one hydrocephalus patients and 21 matched controls completed the study, and their data were used in the final analysis. The authors found significantly lower FA for patients than for controls in 20 of the 48 regions, mostly posterior white matter structures, in periventricular as well as more distal tracts. Of these 20 regions, 17 demonstrated increased RD, while only 5 showed increased MD and 3 showed decreased AD. No areas of increased FA were observed. Higher FA in specific periventricular white matter tracts, tending toward FA in controls, was associated with increased ventricular size, as well as improved clinical outcome.CONCLUSIONSThe study shows that TBSS-based DTI is a sensitive technique for elucidating changes in white matter structures due to hydrocephalus and chronic CSF shunting and provides preliminary evidence that DTI may be a valuable tool for tailoring shunt procedures to monitor ventricular size following shunting and achieve optimal outcome, as well as for guiding the development of alternate therapies for hydrocephalus.

Visual pathway impairment by pituitary adenomas: quantitative diagnostics by diffusion tensor imaging.

OBJECTIVE Despite ample experience in surgical treatment of pituitary adenomas, little is known about objective indices that may reveal risk of visual impairment caused by tumor growth that leads to compression of the anterior visual pathways. This study aimed to explore diffusion tensor imaging (DTI) as a means for objective assessment of injury to the anterior visual pathways caused by pituitary adenomas. METHODS Twenty-three patients with pituitary adenomas, scheduled for transsphenoidal tumor resection, and 20 healthy control subjects were included in the study. A minimum suprasellar tumor extension of Grade 2-4, according to the SIPAP (suprasellar, infrasellar, parasellar, anterior, and posterior) scale, was required for inclusion. Neuroophthalmological examinations, conventional MRI, and DTI were completed in all subjects and were repeated 6 months after surgery. Quantitative assessment of chiasmal lift, visual field defect (VFD), and DTI parameters from the optic tracts was performed. Linear correlations, group comparisons, and prediction models were done in controls and patients. RESULTS Both the degree of VFD and chiasmal lift were significantly correlated with the radial diffusivity (r = 0.55, p < 0.05 and r = 0.48, p < 0.05, respectively) and the fractional anisotropy (r = -0.58, p < 0.05 and r = -0.47, p < 0.05, respectively) but not with the axial diffusivity. The axial diffusivity differed significantly between controls and patients with VFD, both before and after surgery (p < 0.05); however, no difference was found between patients with and without VFD. Based on the axial diffusivity and fractional anisotropy, a prediction model classified all patients with VFD correctly (sensitivity 1.0), 9 of 12 patients without VFD correctly (sensitivity 0.75), and 17 of 20 controls as controls (specificity 0.85). CONCLUSIONS DTI could detect pathology and degree of injury in the anterior visual pathways that were compressed by pituitary adenomas. The correlation between radial diffusivity and visual impairment may reflect a gradual demyelination in the visual pathways caused by an increased tumor effect. The low level of axial diffusivity found in the patient group may represent early atrophy in the visual pathways, detectable on DTI but not by conventional methods. DTI may provide objective data, detect early signs of injury, and be an additional diagnostic tool for determining indication for surgery in cases of pituitary adenomas.

Diffusion tensor imaging as a biomarker for assessing neuronal stem cell treatments affecting areas distal to the site of spinal cord injury.

OBJECTIVE The aims of this study were to determine if the morphological and functional changes induced by neural stem cell (NSC) grafts after transplantation into the rodent spinal cord can be detected using MR diffusion tensor imaging (DTI) and, furthermore, if the DTI-derived mean diffusivity (MD) metric could be a biomarker for cell transplantation in spinal cord injury (SCI). METHODS A spinal contusion was produced at the T-8 vertebral level in 40 Sprague Dawley rats that were separated into 4 groups, including a sham group (injury without NSC injection), NSC control group (injury with saline injection), co-injection control group (injury with Prograf), and the experimental group (injury with NSC and Prograf injection). The NSC injection was completed 1 week after injury into the site of injury and the rats in the experimental group were compared to the rats from the sham, NSC control, and co-injection groups. The DTI index, MD, was assessed in vivo at 2, 5, and 10 weeks and ex vivo at 10 weeks postinjury on a 9.4-T Bruker scanner using a spin-echo imaging sequence. DTI data of the cervical spinal cord from the sham surgery, injury with saline injection, injury with injection of Prograf only, and injury with C17.2 NSC and Prograf injection were examined to evaluate if cellular proliferation induced by intrathoracic C17.2 engraftment was detectable in a noninvasive manner. RESULTS At 5 weeks after injury, the average fractional anisotropy, longitudinal diffusion (LD) and radial diffusion (RD) coefficients, and MD of water (average of the RD and LD eigenvalues in the stem cell line-treated group) increased to an average of 1.44 × 10-3 sec/mm2 in the cervical segments, while the control groups averaged 0.98 × 10-3 s/mm2. Post hoc Tukey's honest significant difference tests demonstrated that the transplanted stem cells had significantly higher MD values than the other groups (p = 0.032 at 5 weeks). In vivo and ex vivo findings at 10 weeks displayed similar results. This statistical difference between the stem cell line and the other groups was maintained at the 10-week postinjury in vivo and ex vivo time points. CONCLUSIONS These results indicate that the DTI-derived MD metric collected from noninvasive imaging techniques may provide useful biomarker indices for transplantation interventions that produce changes in the spinal cord structure and function. Though promising, the results demonstrated here suggest additional work is needed before implementation in a clinical setting.

A preliminary study of the clinical application of optic pathway diffusion tensor tractography in suprasellar tumor surgery: preoperative, intraoperative, and postoperative assessment.

OBJECT Visual impairments are the most common objective manifestations of suprasellar lesions. Diffusion tensor imaging (DTI) is a noninvasive MRI modality that depicts the subcortical white matter tracts in vivo. In this study the authors tested the value of visual pathway tractography in comparison with visual field and visual acuity analyses. METHODS This prospective study consisted of 25 patients with progressive visual impairment due to suprasellar mass lesions and 6 control patients with normal vision without such lesions. Visual acuity, visual field, and the optic fundus were examined preoperatively and repeated 1 week and 3 months after surgery. Visual pathway DTI tractography was performed preoperatively, intraoperatively immediately after tumor resection, and 1 week and 3 months after surgery. RESULTS In the control group, pre- and postoperative visual status were normal and visual pathway tractography revealed fibers crossing the optic chiasm without any alteration. In patients with suprasellar lesions, vision improved in 24 of 25. The mean distance between optic tracts in tractography decreased after tumor resection and detectable fibers crossing the optic chiasm increased from 12% preoperatively to 72% postoperatively 3 months after tumor resection, and undetectable fibers crossing the optic chiasm decreased from 88% preoperatively to 27% postoperatively 3 months after tumor resection. Visual improvement after tumor removal 1 week and 3 months after surgery was significantly correlated with the distance between optic tracts in intraoperative tractography (p < 0.01). CONCLUSIONS Visual pathway DTI tractography appears to be a promising adjunct to the standard clinical and paraclinical visual examinations in patients with suprasellar mass lesions. The intraoperative findings, in particular the distance between optic tract fibers, can predict visual outcome after tumor resection. Furthermore, postoperative application of this technique may be useful in following anterior optic pathway recovery.

Prognostic value of diffusion tensor imaging parameters for Gamma Knife radiosurgery in meningiomas.

OBJECTIVE Diffusion tensor imaging (DTI) parameters are able to differentiate between meningioma subtypes. The hypothesis that there is a correlation between DTI parameters and the change in tumor size after Gamma Knife radiosurgery (GKRS) was analyzed. METHODS DTI parameters were measured using MRI before GKRS in 26 patients with meningiomas. The findings were correlated with the change in tumor size after treatment as measured at the last follow-up (range 12.5-45 months). RESULTS Only those meningiomas that showed the highest fractional anisotropy (FA), the lowest spherical index of the tensor ellipsoid (Cs), and the lowest radial diffusivity (RD) either increased or remained stable in terms of volume, whereas all other meningiomas decreased in volume. The correlation between the DTI parameters (correlation values of -0.81 for FA, 0.75 for Cs, 0.66 for RD, and 0.66 for mean diffusivity) and the rate of volume change per month was significant (p ≤ 0.001). Other factors, including original tumor size, prescription dose, and patient age, did not correlate significantly. CONCLUSIONS Meningiomas that show high FA values-as well as low Cs, low RD, and low mean diffusivity values-do not respond as well to GKRS in comparison with meningiomas with low FA values. This finding might be due to their higher content level of fibrous tissue. In particular, the meningioma with the highest FA value (0.444) considerably increased in volume (by 32.3% after 37 months), whereas the meningioma with the lowest FA value (0.151) showed the highest rate of reduction (3.3% per month) in this study.

Vulnerability of white matter to insult during childhood: evidence from patients treated for medulloblastoma.

OBJECTIVE Craniospinal irradiation damages the white matter in children treated for medulloblastoma, but the treatment-intensity effects are unclear. In a cross-sectional retrospective study, the effects of treatment with the least intensive radiation protocol versus protocols that delivered more radiation to the brain, in addition to the effects of continuous radiation dose, on white matter architecture were evaluated. METHODS Diffusion tensor imaging was used to assess fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity. First, regional white matter analyses and tract-based spatial statistics were conducted in 34 medulloblastoma patients and 38 healthy controls. Patients were stratified according to those treated with 1) the least intensive radiation protocol, specifically reduced-dose craniospinal irradiation plus a boost to the tumor bed only (n = 17), or 2) any other dose and boost combination that delivered more radiation to the brain, which was also termed the "all-other-treatments" group (n = 17), and comprised patients treated with standard-dose craniospinal irradiation plus a posterior fossa boost, standard-dose craniospinal irradiation plus a tumor bed boost, or reduced-dose craniospinal irradiation plus a posterior fossa boost. Second, voxel-wise dose-distribution analyses were conducted on a separate cohort of medulloblastoma patients (n = 15). RESULTS The all-other-treatments group, but not the reduced-dose craniospinal irradiation plus tumor bed group, had lower fractional anisotropy and higher radial diffusivity than controls in all brain regions (all p < 0.05). The reduced-dose craniospinal irradiation plus tumor bed boost group had higher fractional anisotropy (p = 0.05) and lower radial diffusivity (p = 0.04) in the temporal region, and higher fractional anisotropy in the frontal region (p = 0.04), than the all-other-treatments group. Linear mixed-effects modeling revealed that the dose and age at diagnosis together 1) better predicted fractional anisotropy in the temporal region than models with either alone (p < 0.005), but 2) did not better predict fractional anisotropy in comparison with dose alone in the occipital region (p > 0.05). CONCLUSIONS Together, the results show that white matter damage has a clear association with increasing radiation dose, and that treatment with reduced-dose craniospinal irradiation plus tumor bed boost appears to preserve white matter in some brain regions.