Antonella Castellano

Motor and language DTI Fiber Tracking combined with intraoperative subcortical mapping for surgical removal of gliomas

Preoperative DTI Fiber Tracking (DTI-FT) reconstruction of functional tracts combined with intraoperative subcortical mapping (ISM) is potentially useful to improve surgical procedures in gliomas located in eloquent areas. Aims of the study are: (1) to evaluate the modifications of fiber trajectory induced by the tumor; (2) to validate preoperative DTI-FT results with intraoperative identification of functional subcortical sites through direct subcortical stimulation; (3) to evaluate the impact of preoperative DTI-FT reconstructions in a neuronavigational setup combined with ISM technique on duration and modalities of surgical procedures, and on functional outcome of the patients. Data are available on 64 patients (52 low-grade and 12 high-grade gliomas). DTI-FT was acquired by a 3-T MR scanner with a single-shot EPI sequence (TR/TE 8986/80 ms, b=1000 s/mm) with gradients applied along 32 non-collinear directions. 3D Fast Field Echo (FFE) T1-weighted imaging (TR/TE 8/4 ms) was performed for anatomic guidance. The corticospinal tract (CST), superior longitudinal, inferior fronto-occipital and uncinatus fasciculi were reconstructed. Data were transferred to the neuronavigational system. Functional subcortical sites identified during ISM were correlated with fiber tracts depicted by DTI-FT. In high-grade gliomas, DTI-FT depicted tracts mostly at the tumor periphery; in low-grade gliomas, fibers were frequently located inside the tumor mass. There was a high correlation between DTI-FT and ISM (sensitivity for CST=95%, language tracts=97%). For a proper reconstruction of the tracts, it was necessary to use a low FA threshold of fiber tracking algorithm and to position additional regions of interest (ROIs). The combination of DTI-FT and ISM decreased the duration of surgery, patient fatigue, and intraoperative seizures. Combination of DTI-FT and ISM allows accurate identification of eloquent fiber tracts and enhances surgical performance and safety maintaining a high rate of functional preservation.

What is the role of the uncinate fasciculus? Surgical removal and proper name retrieval

The functional role of the uncinate fasciculus is still a matter of debate. We examined 44 patients submitted to awake surgery for removal of a left frontal or temporal glioma. In 18 patients, the removal included the uncinate fasciculus. We compared patients with or without removal on a series of neuropsychological tasks, performed at different time intervals: pre-surgery, in the first week after surgery and 3 months after surgery. Functional magnetic resonance and diffusion tensor imaging, fibre-tracking techniques were performed before surgery. At the last examination, patients with uncinate removal were significantly impaired in naming of famous faces and objects as compared with patients without removal. We further divided patients according to the site of the tumour (either frontal or temporal). At the follow-up, patients with a temporal glioma who underwent uncinate removal had the worst loss of performance in famous face naming. In addition, on the same task, the group with a frontal glioma that underwent resection of the frontal part of the uncinate performed significantly worse than the group with a frontal glioma but without uncinate removal. In conclusion, the resection of the uncinate fasciculus, in its frontal or temporal part, has long-lasting consequences for famous face naming. We suggest that this fibre tract is part of a circuitry involved in the retrieval of word form for proper names. Retrieval of conceptual knowledge was intact.

Intraoperative use of diffusion tensor imaging fiber tractography and subcortical mapping for resection of gliomas: technical considerations

Resection of lesions involving motor or language areas or pathways requires the intraoperative identification of functional cortical and subcortical sites for effectively and safe guidance. Diffusion tensor (DT) imaging and fiber tractography are MR imaging techniques based on the concept of anisotropic water diffusion in myelinated fibers, which enable 3D reconstruction and visualization of white matter tracts and provide information about the relationship of these tracts to the tumor mass. The authors routinely used DT imaging fiber tractography to reconstruct various tracts involved in the motor and/or language system in a large series of patients with lesions involving the motor and/or language areas or pathways. The DT imaging fiber tractography data were loaded into the neuronavigational system and combined intraoperatively with those obtained from direct electrical stimulation applied at the subcortical level. In this paper the authors report the results of their experience, describing the findings for each tract and discussing technical aspects of the combined use as well as the pitfalls.

Role of diffusion tensor magnetic resonance tractography in predicting the extent of resection in glioma surgery

Diffusion tensor imaging (DTI) tractography enables the in vivo visualization of the course of white matter tracts inside or around a tumor, and it provides the surgeon with important information in resection planning. This study is aimed at assessing the ability of preoperative DTI tractography in predicting the extent of the resection achievable in surgical removal of gliomas. Patients with low-grade gliomas (LGGs; 46) and high-grade gliomas (HGGs; 27) were studied using a 3T scanner according to a protocol including a morphological study (T2, fluid-attenuated inversion-recovery, T1 sequences) and DTI acquisitions (b = 1000 s/mm(2), 32 gradient directions). Preoperative tractography was performed off-line on the basis of a streamline algorithm, by reconstructing the inferior fronto-occipital (IFO), the superior longitudinal fascicle (SLF), and the corticospinal tract (CST). For each patient, the relationship between each bundle reconstructed and the lesion was analyzed. Initial and residual tumor volumes were measured on preoperative and postoperative 3D fluid-attenuated inversion-recovery images for LGGs and postcontrast T1-weighted scans for HGGs. The presence of intact fascicles was predictive of a better surgical outcome, because these cases showed a higher probability of total resection than did subtotal and partial resection. The presence of infiltrated or displaced CST or infiltrated IFO was predictive of a lower probability of total resection, especially for tumors with preoperative volume <100 cm(3). DTI tractography can thus be considered to be a promising tool for estimating preoperatively the degree of radicality to be reached by surgical resection. This information will aid clinicians in identifying patients who will mostly benefit from surgery.

Connectivity constraints on cortical reorganization of neural circuits involved in object naming

The brains plasticity in response to sensory deprivation and other perturbations is well established. While the functional properties of the reorganized areas are under vigorous investigation, the factors that constrain cortical reorganization remain poorly understood. One factor constraining such reorganization may be long-distance subcortical connectivity between relevant cortical regions-reorganization attempts to preserve the functionality of subcortical connections. Here we provide human neurophysiological evidence for the role of the subcortical connections in shaping cortical reorganization of the networks involved in object naming following perturbation of normal function. We used direct electrical stimulation (DES) during surgical removal of gliomas to identify the sites that are involved in naming different categories of objects. The sites that were selectively inhibited in naming either living or non-living objects were displaced relative to those observed with other subject populations, possibly reflecting cortical reorganization due to slowly evolving brain damage. Subcortical DES applied to the white matter underlying these regions also led to category-specific naming deficits. The existence of these subcortical fiber pathways was confirmed using diffusion tensor tractography. These results constitute the first neurophysiological evidence for the critical role of subcortical pathways as part of the neural circuits that are involved in object naming; they also highlight the importance of subcortical connectivity in shaping cortical reorganization following perturbations of normal function.

Cerebral Correlates of Visuospatial Neglect: A Direct Cerebral Stimulation Study

To assess the role of the superior longitudinal fascicle, the inferior fronto‐occipital fascicle, and the posterior parietal lobe in visuospatial attention in humans during awake brain surgery.

Tailoring neurophysiological strategies with clinical context enhances resection and safety and expands indications in gliomas involving motor pathways

BACKGROUND Resection of motor pathway gliomas requires the intraoperative recognition of essential cortical-subcortical motor structures. The degree of involvement of motor structures is variable, and increases as result of treatments patients are submitted to. Intraoperative neurophysiology offers various stimulation modalities, which efficiency is based on the ability to recognize essential sites with the highest possible resolution in most clinical conditions. Two stimulation paradigms evolved for intraoperative guidance of motor tumors removal: the 60 Hz-technique [low frequency (LF)] and the pulse-technique [high frequency-(HF)], delivered by bipolar or monopolar probe respectively. Most surgical teams rely on to either of the 2 techniques. The key point is the integration of the choice of the stimulation modality with the clinical context. METHODS In 591 tumors involving the corticospinal tract, the use of HF and LF was tailored to the clinical context defined by patient clinical history and tumor features (by imaging). The effect was evaluated on the feasibility of mapping, the impact on immediate and permanent morbidity, the extent of resection, and the number of patients treated. RESULTS By integrating the choice of the probe and the stimulation protocol with patient clinical history and tumor characteristics, the best probe-frequency match was identified for the different sets of clinical conditions. This integrative approach allows increasing the extent of resection and patient functional integrity, and greatly expands the number of patients who could benefit from surgery. CONCLUSIONS The integration of stimulation modalities with clinical context enhances the extent and safety of resection and expands the population of patients who could benefit from surgical treatment.

Association between thoracic spinal cord gray matter atrophy and disability in multiple sclerosis

IMPORTANCE In multiple sclerosis (MS), upper cervical cord gray matter (GM) atrophy correlates more strongly with disability than does brain or cord white matter (WM) atrophy. The corresponding relationships in the thoracic cord are unknown owing to technical difficulties in assessing GM and WM compartments by conventional magnetic resonance imaging techniques. OBJECTIVES To investigate the associations between MS disability and disease type with lower thoracic cord GM and WM areas using phase-sensitive inversion recovery magnetic resonance imaging at 3 T, as well as to compare these relationships with those obtained at upper cervical levels. DESIGN, SETTING, AND PARTICIPANTS Between July 2013 and March 2014, a total of 142 patients with MS (aged 25-75 years; 86 women) and 20 healthy control individuals were included in this cross-sectional observational study conducted at an academic university hospital. MAIN OUTCOMES AND MEASURES Total cord areas (TCAs), GM areas, and WM areas at the disc levels C2/C3, C3/C4, T8/9, and T9/10. Area differences between groups were assessed, with age and sex as covariates. RESULTS Patients with relapsing MS (RMS) had smaller thoracic cord GM areas than did age- and sex-matched control individuals (mean differences [coefficient of variation (COV)]: 0.98 mm2 [9.2%]; P = .003 at T8/T9 and 0.93 mm2 [8.0%]; P = .01 at T9/T10); however, there were no significant differences in either the WM area or TCA. Patients with progressive MS showed smaller GM areas (mean differences [COV]: 1.02 mm2 [10.6%]; P < .001 at T8/T9 and 1.37 mm2 [13.2%]; P < .001 at T9/T10) and TCAs (mean differences [COV]: 3.66 mm2 [9.0%]; P < .001 at T8/T9 and 3.04 mm2 [7.2%]; P = .004 at T9/T10) compared with patients with RMS. All measurements (GM, WM, and TCA) were inversely correlated with Expanded Disability Status Scale score. Thoracic cord GM areas were correlated with lower limb function. In multivariable models (which also included cord WM areas and T2 lesion number, brain WM volumes, brain T1 and fluid-attenuated inversion recovery lesion loads, age, sex, and disease duration), cervical cord GM areas had the strongest correlation with Expanded Disability Status Scale score followed by thoracic cord GM area and brain GM volume. CONCLUSIONS AND RELEVANCE Thoracic cord GM atrophy can be detected in vivo in the absence of WM atrophy in RMS. This atrophy is more pronounced in progressive MS than RMS and correlates with disability and lower limb function. Our results indicate that remarkable cord GM atrophy is present at multiple cervical and lower thoracic levels and, therefore, may reflect widespread cord GM degeneration.

Dynamic contrast-enhanced and dynamic susceptibility contrast perfusion MR imaging for glioma grading: Preliminary comparison of vessel compartment and permeability parameters using hotspot and histogram analysis

INTRODUCTION Dynamic susceptibility contrast (DSC)-MRI is a perfusion technique with high diagnostic accuracy for glioma grading, despite limitations due to inherent susceptibility effects. Dynamic contrast-enhanced (DCE)-MRI has been proposed as an alternative technique able to overcome the DSC-MRI shortcomings. This pilot study aimed at comparing the diagnostic accuracy of DSC and DCE-MRI for glioma grading by evaluating two estimates of blood volume, the DCE-derived plasma volume (Vp) and the DSC-derived relative cerebral blood volume (rCBV), and a measure of vessel permeability, the DCE-derived volume transfer constant K(trans). METHODS Twenty-six newly diagnosed glioma patients underwent 3T-MR DCE and DSC imaging. Parametric maps of CBV, Vp and K(trans) were calculated and the region of highest value (hotspot) was measured on each map. Histograms of rCBV, Vp and K(trans) values were calculated for the tumor volume. Statistical differences according to WHO grade were assessed. The diagnostic accuracy for tumor grading of the two techniques was determined by ROC analysis. RESULTS rCBV, Vp and K(trans) measures differed significantly between high and low-grade gliomas. Hotspot analysis showed the highest correlation with grading. K(trans) hotspots co-localized with Vp hotspots only in 56% of enhancing gliomas. For differentiating high from low-grade gliomas the AUC was 0.987 for rCBVmax, and 1.000 for Vpmax and K(trans)max. Combination of DCE-derived Vp and K(trans) parameters improved the diagnostic performance of the histogram method. CONCLUSION This initial experience of DCE-derived Vp evaluation shows that this parameter is as accurate as the well-established DSC-derived rCBV for glioma grading. DCE-derived K(trans) is equally useful for grading, providing different informations with respect to Vp.

Quantitative MRI of the spinal cord and brain in adrenomyeloneuropathy: in vivo assessment of structural changes.

Adrenomyeloneuropathy is the late-onset form of X-linked adrenoleukodystrophy, and is considered the most frequent metabolic hereditary spastic paraplegia. In adrenomyeloneuropathy the spinal cord is the main site of pathology. Differently from quantitative magnetic resonance imaging of the brain, little is known about the feasibility and utility of advanced neuroimaging in quantifying the spinal cord abnormalities in hereditary diseases. Moreover, little is known about the subtle pathological changes that can characterize the brain of adrenomyeloneuropathy subjects in the early stages of the disease. We performed a cross-sectional study on 13 patients with adrenomyeloneuropathy and 12 age-matched healthy control subjects who underwent quantitative magnetic resonance imaging to assess the structural changes of the upper spinal cord and brain. Total cord areas from C2-3 to T2-3 level were measured, and diffusion tensor imaging metrics, i.e. fractional anisotropy, mean, axial and radial diffusivity values were calculated in both grey and white matter of spinal cord. In the brain, grey matter regions were parcellated with Freesurfer and average volume and thickness, and mean diffusivity and fractional anisotropy from co-registered diffusion maps were calculated in each region. Brain white matter diffusion tensor imaging metrics were assessed using whole-brain tract-based spatial statistics, and tractography-based analysis on corticospinal tracts. Correlations among clinical, structural and diffusion tensor imaging measures were calculated. In patients total cord area was reduced by 26.3% to 40.2% at all tested levels (P < 0.0001). A mean 16% reduction of spinal cord white matter fractional anisotropy (P ≤ 0.0003) with a concomitant 9.7% axial diffusivity reduction (P < 0.009) and 34.5% radial diffusivity increase (P < 0.009) was observed, suggesting co-presence of axonal degeneration and demyelination. Brain tract-based spatial statistics showed a marked reduction of fractional anisotropy, increase of radial diffusivity (P < 0.001) and no axial diffusivity changes in several white matter tracts, including corticospinal tracts and optic radiations, indicating predominant demyelination. Tractography-based analysis confirmed the results within corticospinal tracts. No significant cortical volume and thickness reduction or grey matter diffusion tensor imaging values alterations were observed in patients. A correlation between radial diffusivity and disease duration along the corticospinal tracts (r = 0.806, P < 0.01) was found. In conclusion, in adrenomyeloneuropathy patients quantitative magnetic resonance imaging-derived measures identify and quantify structural changes in the upper spinal cord and brain which agree with the expected histopathology, and suggest that the disease could be primarily caused by a demyelination rather than a primitive axonal damage. The results of this study may also encourage the employment of quantitative magnetic resonance imaging in other hereditary diseases with spinal cord involvement.