Resection of supplementary motor area gliomas: revisiting supplementary motor syndrome and the role of the frontal aslant tract

J Neurosurg 136:1278–1284, 2022

The supplementary motor area (SMA) is an eloquent region that is frequently a site for glioma, or the region is included in the resection trajectory to deeper lesions. Although the clinical relevance of SMA syndrome has been well described, it is still difficult to predict who will become symptomatic. The object of this study was to define which patients with SMA gliomas would go on to develop a postoperative SMA syndrome.

METHODS The University of California, San Francisco, tumor registry was searched for patients who, between 2010 and 2019, had undergone resection for newly diagnosed supratentorial diffuse glioma (WHO grades II–IV) performed by the senior author and who had at least 3 months of follow-up. Pre- and postoperative MRI studies were reviewed to confirm the tumor was located in the SMA region, and the extent of SMA resection was determined by volumetric assessment. Patient, tumor, and outcome data were collected retrospectively from documents available in the electronic medical record. Tumors were registered to a standard brain atlas to create a frequency heatmap of tumor volumes and resection cavities.

RESULTS During the study period, 56 patients (64.3% male, 35.7% female) underwent resection of a newly diagnosed glioma in the SMA region. Postoperatively, 60.7% developed an SMA syndrome. Although the volume of tumor within the SMA region did not correlate with the development of SMA syndrome, patients with the syndrome had larger resection cavities in the SMA region (25.4% vs 14.2% SMA resection, p = 0.039). The size of the resection cavity in the SMA region did not correlate with the severity of the SMA syndrome. Patients who developed the syndrome had cavities that were located more posteriorly in the SMA region and in the cingulate gyrus. When the frontal aslant tract (FAT) was preserved, 50% of patients developed the SMA syndrome postoperatively, whereas 100% of the patients with disruption of the FAT during surgery developed the SMA syndrome (p = 0.06). Patients with SMA syndrome had longer lengths of stay (5.6 vs 4.1 days, p = 0.027) and were more likely to be discharged to a rehabilitation facility (41.9% vs 0%, p < 0.001). There was no difference in overall survival for newly diagnosed glioblastoma patients with SMA syndrome compared to those without SMA syndrome (1.6 vs 3.0 years, p = 0.33).

CONCLUSIONS For patients with SMA glioma, more extensive resections and resections involving the posterior SMA region and posterior cingulate gyrus increased the likelihood of a postoperative SMA syndrome. Although SMA syndrome occurred in all cases in which the FAT was resected, FAT preservation does not reliably avoid SMA syndrome postoperatively.


Classifier Using Pontine Radial Diffusivity and Symptom Duration Accurately Predicts Recurrence of Trigeminal Neuralgia After Microvascular Decompression

Neurosurgery 89:777–783, 2021

Preprocedure diffusion tensor magnetic resonance imaging (MRI) may predict the response of trigeminal neuralgia (TN) patients to Gamma Knife (Elekta AB) and microvascular decompression (MVD).

OBJECTIVE: To test this hypothesis using pontine-segment diffusion tensor MRI radial diffusivity (RD), a known biomarker for demyelination, to predict TN recurrence following MVD.

METHODS: RD from the pontine segment of the trigeminal tract was extracted in a semiautomated and blinded fashion and normalized to background pontine RD. Following validation against published results, the relationship of normalized RD to symptom duration (DS)was measured. Both parameterswere then introduced intomachine-learning classifiers to group patient outcomes as TN remission or recurrence. Performance was evaluated in an observational study with leave-one-out cross-validation to calculate accuracy, sensitivity, specificity, and receiver operating characteristic curves.

RESULTS: The study population included 22 patients with TN type 1 (TN1). There was a negative correlation of normalized RD and preoperative symptom duration (P = .035, R2 = .20). When pontine-segment RD and DS were included as input variables, 2 classifiers predicted pain-free remission versus eventual recurrence with 85% accuracy, 83% sensitivity, and 86% specificity (leave-one-out cross-validation; P = .029) in a cohort of 13 patients undergoing MVD.

CONCLUSION: Pontine-segment RD and DS accurately predict MVD outcomes in TN1 and provide further evidence that diffusion tensor MRI contains prognostic information. Use of a classifier may allow more accurate risk stratification for neurosurgeons and patients considering MVD as a treatment for TN1. These findings provide further insight into the relationship of pontine microstructure, represented by RD, and the pathophysiology of TN.


Functional DTI tractography in brainstem cavernoma surgery

J Neurosurg 135:712–721, 2021

Surgical resection of brainstem cavernomas is associated with high postoperative morbidity due to the density of local vulnerable structures. Classical mapping of pathways by diffusion tensor imaging (DTI) has proven to be unspecific and confusing in many cases. In the current study, the authors aimed to establish a more reliable, specific, and objective method for somatotopic visualization of the descending motor pathways with navigated transcranial magnetic stimulation (nTMS)–based DTI fiber tracking.

METHODS Twenty-one patients with brainstem cavernomas were examined with nTMS prior to surgery. The resting motor threshold (RMT) and cortical representation areas of hand, leg, and facial function were determined on both hemispheres. Motor evoked potential (MEP)–positive stimulation spots were then set as seed points for tractography. Somatotopic fiber tracking was performed at a fractional anisotropy (FA) value of 75% of the individual FA threshold.

RESULTS Mapping of the motor cortex and tract reconstruction for hand, leg, and facial function was successful in all patients. The somatotopy of corticospinal and corticonuclear tracts was also clearly depicted on the brainstem level. Higher preoperative RMT values were associated with a postoperative motor deficit (p < 0.05) and correlated with a lower FA threshold (p < 0.05), revealing structural impairment of the corticospinal tract (CST) prior to surgery. In patients with a new deficit, the distance between the lesion and CST was below 1 mm.

CONCLUSIONS nTMS-based fiber tracking enables objective somatotopic tract visualization on the brainstem level and provides a valuable instrument for preoperative planning, intraoperative orientation, and individual risk stratification. nTMS may thus increase the safety of surgical resection of brainstem cavernomas.


Language hemispheric dominance analyzed with magnetic resonance DTI: correlation with the Wada test

J Neurosurg 134:1703–1710, 2021

Language lateralization is a major concern in some patients with pharmacoresistant epilepsy who will face surgery; in these patients, hemispheric dominance testing is essential to avoid further complications. The Wada test is considered the gold standard examination for language localization, but is invasive and requires many human and material resources. Functional MRI and tractography with diffusion tensor imaging (DTI) have demonstrated that they could be useful for locating language in epilepsy surgery, but there is no evidence of the correlation between the Wada test and DTI MRI in language dominance.

METHODS The authors performed a retrospective review of patients who underwent a Wada test before epilepsy surgery at their institution from 2012 to 2017. The authors retrospectively analyzed fractional anisotropy (FA), number and length of fibers, and volume of the arcuate fasciculus and uncinate fasciculus, comparing dominant and nondominant hemispheres.

RESULTS Ten patients with temporal lobe epilepsy were reviewed. Statistical analysis showed that the mean FA of the arcuate fasciculus in the dominant hemisphere was higher than in the nondominant hemisphere (0.369 vs 0.329, p = 0.049). Also, the number of fibers in the arcuate fasciculus was greater in the dominant hemisphere (881.5 vs 305.4, p = 0.003). However, no differences were found in the FA of the uncinate fasciculus or number of fibers between hemispheres. The length of fibers of the uncinate fasciculus was longer in the dominant side (74.4 vs 50.1 mm, p = 0.05). Volume in both bundles was more prominent in the dominant hemisphere (12.12 vs 6.48 cm3, p = 0.004, in the arcuate fasciculus, and 8.41 vs 4.16 cm3, p = 0.018, in the uncinate fasciculus). Finally, these parameters were compared in patients in whom the seizure focus was situated in the dominant hemisphere: FA (0.37 vs 0.30, p = 0.05), number of fibers (114.4 vs 315.6, p = 0.014), and volume (12.58 vs 5.88 cm3, p = 0.035) in the arcuate fasciculus were found to be statistically significantly higher in the dominant hemispheres. Linear discriminant analysis of FA, number of fibers, and volume of the arcuate fasciculus showed a correct discrimination in 80% of patients (p = 0.024).

CONCLUSIONS The analysis of the arcuate fasciculus and other tract bundles by DTI could be a useful tool for language location testing in the preoperative study of patients with refractory epilepsy.

Deep brain stimulation for aggressiveness: long-term follow-up and tractography study of the stimulated brain areas

J Neurosurg 134:366–375, 2021

Initial studies applying deep brain stimulation (DBS) of the posteromedial hypothalamus (PMH) to patients with pathological aggressiveness have yielded encouraging results. However, the anatomical structures involved in its therapeutic effect have not been precisely identified. The authors’ objective was to describe the long-term outcome in their 7-patient series, and the tractography analysis of the volumes of tissue activated in 2 of the responders.

METHODS This was a retrospective study of 7 subjects with pathological aggressiveness. The findings on MRI with diffusion tensor imaging (DTI) in 2 of the responders were analyzed. The authors generated volumes of tissue activated according to the parameters used, and selected those volumes as regions of interest to delineate the tracts affected by stimulation.

RESULTS The series consisted of 5 men and 2 women. Of the 7 patients, 5 significantly improved with stimulation. The PMH, ventral tegmental area, dorsal longitudinal fasciculus, and medial forebrain bundle seem to be involved in the stimulation field.

CONCLUSIONS In this series, 5 of 7 medication-resistant patients with severe aggressiveness who were treated with bilateral PMH DBS showed a significant long-lasting improvement. The PMH, ventral tegmental area, dorsal longitudinal fasciculus, and medial forebrain bundle seem to be in the stimulation field and might be responsible for the therapeutic effect of DBS.


Predicting the Extent of Resection in Low-Grade Glioma by Using Intratumoral Tractography to Detect Eloquent FasciclesWithin the Tumor

Neurosurgery 88(2) 2021: E190–E202

An early maximal safe surgical resection is the current treatment paradigm for low-grade glioma (LGG). Nevertheless, there are no reliable methods to accurately predict the axonal intratumoral eloquent areas and, consequently, to predict the extent of resection.

OBJECTIVE: To describe the functional predictive value of eloquent white matter tracts within the tumor by using a pre- and postoperative intratumoral diffusion tensor imaging (DTI) tractography protocol in patients with LGG.

METHODS: A preoperative intratumoral DTI-based tractography protocol, using the tumor segmented volume as the only seed region, was used to assess the tracts within the tumor boundaries in 22 consecutive patients with LGG. The reconstructed tracts were correlated with intraoperative electrical stimulation (IES)-based language and motor subcortical mapping findings and the extent of resection was assessed by tumor volumetrics.

RESULTS: Identification of intratumoral language and motor tracts significantly predicted eloquent areas within the tumor during the IES mapping: the positive predictive value for the pyramidal tract, the inferior fronto-occipital fasciculus, the arcuate fasciculus and the inferior longitudinal fasciculus positive was 100%, 100%, 33%, and 80%, respectively, whereas negative predictive value was 100% for all of them. The reconstruction of at least one of these tracts within the tumor was significantly associated with a lower extent of resection (67%) as opposed to the extent of resection in the cases with a negative intratumoral tractography (100%) (P< .0001).

CONCLUSION: Intratumoral DTI-based tractography is a simple and reliable method, useful in assessing glioma resectability based on the analysis of intratumoral eloquent areas associated with motor and language tracts within the tumor.

Tractography-based targeting of the ventral intermediate nucleus

J Neurosurg 133:1002–1009, 2020

Tractography-based targeting of the thalamic ventral intermediate nucleus (T-VIM) is a novel method conferring patient-specific selection of VIM coordinates for tremor surgery; however, its accuracy and clinical utility in magnetic resonance imaging–guided focused ultrasound (MRgFUS) thalamotomy compared to conventional indirect targeting has not been specifically addressed. This retrospective study sought to compare the treatment locations and potential adverse effect profiles of T-VIM with indirect targeting in a large cohort of MRgFUS thalamotomy patients.

METHODS T-VIM was performed using diffusion tractography outlining the pyramidal and medial lemniscus tracts in 43 MRgFUS thalamotomy patients. T-VIM coordinates were compared with the indirect treatment coordinates used in the procedure. Thalamotomy lesions were delineated on postoperative T1-weighted images and displaced (“translated”) by the anteroposterior and mediolateral difference between T-VIM and treatment coordinates. Both translated and actual lesions were normalized to standard space and subsequently overlaid with areas previously reported to be associated with an increased risk of motor and sensory adverse effects when lesioned during MRgFUS thalamotomy.

RESULTS T-VIM coordinates were 2.18 mm anterior and 1.82 mm medial to the “final” indirect treatment coordinates. Translated lesions lay more squarely within the boundaries of the VIM compared to nontranslated lesions and showed significantly less overlap with areas associated with sensory adverse effects. Translated lesions overlapped less with areas associated with motor adverse effects; however, this difference was not significant.

CONCLUSIONS T-VIM leads to the selection of more anterior and medial coordinates than the conventional indirect methods. Lesions moved toward these anteromedial coordinates avoid areas associated with an increased risk of motor and sensory adverse effects, suggesting that T-VIM may improve clinical outcomes.

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

J Neurosurg 133:839–847, 2020

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 mm 2 /second) compared with controls (mean 6.15 × 10 −4 mm 2 / second, p = 0.02). Radial diffusivity was increased ipsilaterally in patients (mean 4.91 × 10 −4 mm 2 /second) compared with controls (mean 4.44 × 10 −4 mm 2 /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.

Diffusion tensor imaging reveals microstructural differences between subtypes of trigeminal neuralgia

J Neurosurg 133:573–579, 2020

Trigeminal neuralgia (TN) is an uncommon idiopathic facial pain syndrome. To assist in diagnosis, treatment, and research, TN is often classified as type 1 (TN1) when pain is primarily paroxysmal and episodic or type 2 (TN2) when pain is primarily constant in character. Recently, diffusion tensor imaging (DTI) has revealed microstructural changes in the symptomatic trigeminal root and root entry zone of patients with unilateral TN. In this study, the authors explored the differences in DTI parameters between subcategories of TN, specifically TN1 and TN2, in the pontine segment of the trigeminal tract.

METHODS The authors enrolled 8 patients with unilateral TN1, 7 patients with unilateral TN2, and 23 asymptomatic controls. Patients underwent DTI with parameter measurements in a region of interest within the pontine segment of the trigeminal tract. DTI parameters were compared between groups.

RESULTS In the pontine segment, the radial diffusivity (p = 0.0049) and apparent diffusion coefficient (p = 0.023) values in TN1 patients were increased compared to the values in TN2 patients and controls. The DTI measures in TN2 were not statistically significant from those in controls. When comparing the symptomatic to asymptomatic sides in TN1 patients, radial diffusivity was increased (p = 0.025) and fractional anisotropy was decreased (p = 0.044) in the symptomatic sides. The apparent diffusion coefficient was increased, with a trend toward statistical significance (p = 0.066).

CONCLUSIONS Noninvasive DTI analysis of patients with TN may lead to improved diagnosis of TN subtypes (e.g., TN1 and TN2) and improve patient selection for surgical intervention. DTI measurements may also provide insights into prognosis after intervention, as TN1 patients are known to have better surgical outcomes than TN2 patients.


Characterizing tumor invasiveness of glioblastoma using multiparametric magnetic resonance imaging

J Neurosurg 132:1465–1472, 2020

The objective of this study was to characterize the abnormalities revealed by diffusion tensor imaging (DTI) using MR spectroscopy (MRS) and perfusion imaging, and to evaluate the prognostic value of a proposed quantitative measure of tumor invasiveness by combining contrast-enhancing (CE) and DTI abnormalities in patients with glioblastoma.

METHODS Eighty-four patients with glioblastoma were recruited preoperatively. DTI was decomposed into isotropic (p) and anisotropic (q) components. The relative cerebral blood volume (rCBV) was calculated from the dynamic susceptibility contrast imaging. Values of N-acetylaspartate, myoinositol, choline (Cho), lactate (Lac), and glutamate + glutamine (Glx) were measured from multivoxel MRS and normalized as ratios to creatine (Cr). Tumor regions of interest (ROIs) were manually segmented from the CE T1-weighted (CE-ROI) and DTI-q (q-ROI) maps. Perfusion and metabolic characteristics of these ROIs were measured and compared. The relative invasiveness coefficient (RIC) was calculated as a ratio of the characteristic radii of CE-ROI and q-ROI. The prognostic significance of RIC was tested using Kaplan-Meier and multivariate Cox regression analyses.

RESULTS The Cho/Cr, Lac/Cr, and Glx/Cr in q-ROI were significantly higher than CE-ROI (p = 0.004, p = 0.005, and p = 0.007, respectively). CE-ROI had significantly higher rCBV values than q-ROI (p < 0.001). A higher RIC was associated with worse survival in a multivariate overall survival (OS) model (hazard ratio [HR] 1.40, 95% confidence interval [CI] 1.06–1.85, p = 0.016) and progression-free survival (PFS) model (HR 1.55, 95% CI 1.16–2.07, p = 0.003). An RIC cutoff value of 0.89 significantly predicted shorter OS (median 384 vs 605 days, p = 0.002) and PFS (median 244 vs 406 days, p = 0.001).

CONCLUSIONS DTI-q abnormalities displayed higher tumor load and hypoxic signatures compared with CE abnormalities, whereas CE regions potentially represented the tumor proliferation edge. Integrating the extents of invasion visualized by DTI-q and CE images into clinical practice may lead to improved treatment efficacy.

Utility of a Quantitative Approach Using Diffusion Tensor Imaging for Prognostication Regarding Motor and Functional Outcomes in Patients With Surgically Resected Deep Intracranial Cavernous Malformations

Neurosurgery 86:665–675, 2020

Resection of deep intracranial cavernous malformations (CMs) is associated with a higher risk of neurological deterioration and uncertainty regarding clinical outcomes.

OBJECTIVE: To examine diffusion tractography imaging (DTI) data evaluating the corticospinal tract (CST) in relation to motor and functional outcomes in patients with surgically resected deep CMs.

METHODS: Perilesional CST was characterized as disrupted, displaced, or normal. Mean fractional anisotropy (FA) values were obtained for whole ipsilateral CST and in 3 regions: subcortical (proximal), perilesional, and distally. Mean FA values in anatomically equivalent regions in the contralateral CST were obtained. Clinical and radiological data were collected independently.Multivariable regression analysis was used for statistical analysis.

RESULTS: A total of 18 patients [brainstem (15) and thalamus/basal ganglia (3); median follow-up: 270 d] were identified over 2 yr. The CST was identified preoperatively as disrupted (6), displaced (8), and normal (4). Five of 6 patientswith disruption hadweakness. Higher preoperative mean FA values for distal ipsilateral CST segmentwere associated with better preoperative lower (P < .001), upper limb (P = .004), postoperative lower (P = .005), and upper limb (P < .001) motor examination. Preoperative mean FA values for distal ipsilateral CST segment (P = .001) and contralateral perilesional CST segment (P < .001) were negatively associated with postoperative modified Rankin scale scores.

CONCLUSION: Lower preoperative mean FA values for overall and defined CST segments corresponded to worse patient pre- and postoperative motor examination and/or functional status. FA value for the distal ipsilateral CST segment has prognostic potential with respect to clinical outcomes.

Disruption of Frontal Aslant Tract Is Not Associated with Long-Term Postoperative Language Deficits

World Neurosurg. (2020) 133:192-195

The frontal aslant tract (FAT) is a white matter fiber pathway connecting the superior frontal gyrus to the Broca area. This tract in the dominant hemisphere has been shown to play a role in speech initiation and production, and direct subcortical stimulation can induce stuttering and speech arrest in a patient. However, controversy remains as to whether disruption of this pathway will lead to a permanent language deficit and if it is even necessary to map this tract during tumor resections of the dominant frontal lobe.

CASE DESCRIPTION: Here, we report a case of a patient with a lower-grade diffuse glioma invading the dominant FAT that was removed with an asleep craniotomy. In the immediate postoperative state, the patient had a transcortical motor dysphasia and was unable to initiate speech. These immediate language deficits quickly recovered, and the patient was neurologically intact at the time of discharge a few days after surgery.

CONCLUSIONS: Given the high likelihood for a complete neurologic recovery including transient aphasia, we propose that awake mapping for the purpose of identifying the dominant FAT is unnecessary during tumor resection and that disruption of this tract is not associated with any long-term language deficits.

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

J Neurosurg 131:539–548, 2019

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.

Correlation of magnetic resonance diffusion tensor imaging parameters with American Spinal Injury Association score for prognostication and long-term outcomes

Neurosurg Focus 46 (3):E2, 2019

Conventional MRI is routinely used to demonstrate the anatomical site of spinal cord injury (SCI). However, quantitative and qualitative imaging parameters have limited use in predicting neurological outcomes. Currently, there are no reliable neuroimaging biomarkers to predict short- and long-term outcome after SCI.

METHODS A prospective cohort of 23 patients with SCI (19 with cervical SCI [CSCI] and 4 with thoracic SCI [TSCI]) treated between 2007 and 2014 was included in the study. The American Spinal Injury Association (ASIA) score was determined at the time of arrival and at 1-year follow-up. Only 15 patients (12 with CSCI and 3 with TSCI) had 1-year follow-up. Whole-cord fractional anisotropy (FA) was determined at C1–2, following which C1–2 was divided into upper, middle, and lower segments and the corresponding FA value at each of these segments was calculated. Correlation analysis was performed between FA and ASIA score at time of arrival and 1-year follow-up.

RESULTS Correlation analysis showed a positive but nonsignificant correlation (p = 0.095) between FA and ASIA score for all patients (CSCI and TCSI) at the time of arrival. Additional regression analysis consisting of only patients with CSCI showed a significant correlation (p = 0.008) between FA and ASIA score at time of arrival as well as at 1-year follow-up (p = 0.025). Furthermore, in case of patients with CSCI, a significant correlation between FA value at each of the segments (upper, middle, and lower) of C1–2 and ASIA score at time of arrival was found (p = 0.017, p = 0.015, and p = 0.002, respectively).

CONCLUSIONS In patients with CSCI, the measurement of diffusion anisotropy of the high cervical cord (C1–2) correlates significantly with injury severity and long-term follow-up. However, this correlation is not seen in patients with TSCI. Therefore, FA can be used as an imaging biomarker for evaluating neural injury and monitoring recovery in patients with CSCI.


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

Neurosurg Focus 46 (3):E7, 2019

Diffusion 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.

METHODS A 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.

RESULTS Among 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.

CONCLUSIONS DTI 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.


Diffusion tensor imaging and ventricle volume quantification in patients with chronic shunt-treated hydrocephalus

J Neurosurg 129:1611–1622, 2018

The 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.

METHODS Patients 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.

RESULTS Twenty-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.

CONCLUSIONS The 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.


The timing of stereotactic radiosurgery for medically refractory trigeminal neuralgia

Acta Neurochirurgica (2018) 160:977–986

Diffusion tensor imaging (DTI) is a novel MRI technique that enables noninvasive evaluation of microstructural alterations in white matter of brain. Initially, DTI was used in intra- or inter-hemispheric association bundles. Recent technical advances are overcoming the challenges of imaging small white matter bundles, such as the cranial nerves. In this study, we use DTI to shed more light on the microstructure changes in long-standing trigeminal neuralgia. We also utilize DTI to study the effect of early stereotactic radiosurgery (SRS) on the microstructures of the trigeminal nerve and to predict the effectiveness of early SRS in the treatment of medically refractory trigeminal neuralgia (TN).

Methods To analyze the presentation of trigeminal nerve, the DTI was reconstructed in 21 cases pre- and post-SRS. DTI parameters recorded include fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD), linear anisotropy coefficient (Cl), planar anisotropy coefficient (Cp), and spherical anisotropy coefficient (Cs). Comparisons between ipsilateral (symptomatic) and contralateral (asymptomatic) trigeminal nerves and symptomdurations of < 5 and ≧ 5 years were performed.

Results The study cohort comprised 21 patients with TN with a median age of 66 years. Initial adequate facial pain relief (Barrow Neurological Institute facial pain scores I–IIIb) was achieved in 16 (76%) patients. For the pre-SRS DTI findings, ipsilateral trigeminal nerve was associated with higher baseline root entry zone (REZ) Cs compared to contralateral nerve (0.774 vs. 0.743, p = 0.04). Ipsilateral trigeminal nerve with symptoms of < 5 years was associated with higher baseline FA compared to trigeminal nerve with symptoms of ≧ 5 years (0.314 vs. 0.244, p = 0.02). For the post-SRS DTI findings, ipsilateral trigeminal nerves with symptoms of <5 years demonstrated decrease in Cl, while those with symptoms ≧ 5 years demonstrated increase in Cl after SRS at the ipsilateral REZ (− 0.025 vs. 0.018, p = 0.04). At the cisternal segment of ipsilateral trigeminal nerve, symptoms of < 5 years were associated with decreased FA and increased λ2, while symptoms of ≧ 5 years were associated with increased FA and decreased λ2 after SRS (FA − 0.068 vs. 0.031, p = 0.04, λ2 0.0003 vs. − 0.0002, p = 0.02).

Conclusions SRS provides high rates of initial pain relief with moderate rates of facial hypoesthesia. Ipsilateral trigeminal nerve was associated with higher baseline REZ Cs, and baseline FAwas associated with duration of symptoms. There were significant associations between duration of symptoms and changes in ipsilateral REZ Cl, cisternal segment FA, and cisternal segment λ2 after SRS. These preliminary findings serve as comparisons for future studies investigating the use of DTI in radiosurgical planning for patients with TN.

Risk assessment of motor function using nTMS-based tractography

J Neurosurg 128:800–810, 2018

Navigated transcranial magnetic stimulation (nTMS) and diffusion tensor imaging fiber tracking (DTI FT) based on nTMS data are increasingly used for preoperative planning and resection guidance in patients suffering from motor-eloquent brain tumors. The present study explores whether nTMS-based DTI FT can also be used for individual preoperative risk assessment regarding surgery-related motor impairment.

METHODS Data derived from preoperative nTMS motor mapping and subsequent nTMS-based tractography in 86 patients were analyzed. All patients suffered from high-grade glioma (HGG), low-grade glioma (LGG), or intracranial metastasis (MET). In this context, nTMS-based DTI FT of the corticospinal tract (CST) was performed at a range of fractional anisotropy (FA) levels based on an individualized FA threshold ([FAT]; tracking with 50%, 75%, and 100% FAT), which was defined as the highest FA value allowing for visualization of fibers (100% FAT). Minimum lesion-to-CST distances were measured, and fiber numbers of the reconstructed CST were assessed. These data were then correlated with the preoperative, postoperative, and follow-up status of motor function and the resting motor threshold (rMT).

RESULTS At certain FA levels, a statistically significant difference in lesion-to-CST distances was observed between patients with HGG who had no impairment and those who developed surgery-related transient or permanent motor deficits (75% FAT: p = 0.0149; 100% FAT: p = 0.0233). In this context, no patient with a lesion-to-CST distance ≥ 12 mm suffered from any new surgery-related permanent paresis (50% FAT and 75% FAT). Furthermore, comparatively strong negative correlations were observed between the rMT and lesion-to-CST distances of patients with surgery-related transient paresis (Spearman correlation coefficient [rs]; 50% FAT: rs = –0.8660; 75% FAT: rs = –0.8660) or surgery-related permanent paresis (50% FAT: rs = –0.7656; 75% FAT: rs = –0.6763).

CONCLUSIONS This is one of the first studies to show a direct correlation between imaging, clinical status, and neurophysiological markers for the integrity of the motor system in patients with brain tumors. The findings suggest that nTMSbased DTI FT might be suitable for individual risk assessment in patients with HGG, in addition to being a surgery-planning tool. Importantly, necessary data for risk assessment were obtained without significant additional efforts, making this approach potentially valuable for direct clinical use.

Reduced Field-of-View Diffusion Tensor Imaging of the Spinal Cord Shows Motor Dysfunction of the Lower Extremities in Patients With Cervical Compression Myelopathy

Spine 2018;43:89–96

Study Design. A cross-sectional study.

Objective. The aim of this study was to quantify spinal cord dysfunction at the tract level in patients with cervical compressive myelopathy (CCM) using reduced field-of-view (rFOV) diffusion tensor imaging (DTI).

Summary of Background Data. Although magnetic resonance imaging (MRI) is the standard used for radiological evaluation of CCM, information acquired by MRI does not necessarily reflect the severity of spinal cord disorder. There is a growing interest in developing imaging methods to quantify spinal cord dysfunction. To acquire high-resolution DTI, a new scheme using rFOV has been proposed.

Methods. We enrolled 10 healthy volunteers and 20 patients with CCM in this study. The participants were studied using a 3.0-T MRI system. For DTI acquisitions, diffusion-weighted spinecho rFOV single-shot echo-planar imaging was used. Regions of interest (ROI) for the lateral column (LC) and posterior column (PC) tracts were determined on the basis of a map of fractional anisotropy (FA) of the spinal cord and FA values were measured. The FA of patients with CCM was compared with that of healthy controls and correlated with Japanese Orthopaedic Association (JOA) score.

Results. In LC and PC tracts, FA values in patients with CCM were significantly lower than in healthy volunteers. Total JOA scores correlated moderately with FA in LC and PC tracts. JOA subscores for motor dysfunction of the lower extremities correlated strongly with FA in LC and PC tracts.

Conclusion. It is feasible to evaluate the cervical spinal cord at the tract level using rFOV DTI. Although FA values at the maximum compression level were not well correlated with total JOA scores, they were strongly correlated with JOA subscores for motor dysfunction of the lower extremities. Our findings suggest that FA reflects white matter dysfunction below the maximum compression level and FA can be used as an imaging biomarker of spinal cord dysfunction.

Key words: . Level of Evidence: 4

Three-Dimensional Printed Modeling of Diffuse Low-Grade Gliomas and Associated White Matter Tract Anatomy

Neurosurgery 80:635–645, 2017

Diffuse low-grade gliomas (DLGGs) represent several pathological entities that infiltrate and invade cortical and subcortical structures in the brain.

OBJECTIVE: To describe methods for rapid prototyping of DLGGs and surgically relevant anatomy.

METHODS: Using high-definition imaging data and rapid prototyping technologies, we were able to generate 3 patient DLGGs to scale and represent the associated whitematter tracts in 3 dimensions using advanced diffusion tensor imaging techniques.

RESULTS: This report represents a novel application of 3-dimensional (3-D) printing in neurosurgery and a means to model individualized tumors in 3-D space with respect to subcorticalwhite matter tract anatomy. Faculty and resident evaluations of this technology were favorable at our institution.

CONCLUSION: Developing an understanding of the anatomic relationships existing within individuals is fundamental to successful neurosurgical therapy. Imaging-based rapid prototyping may improve on our ability to plan for and treat complex neuro-oncologic pathology.