Namath s. Hussain, M.D. Penn state Hershey neurosurgery The Impact of Intracranial Tumor Proximity to White Matter Tracts on Morbidity and Mortality: A Retrospective DTI Study Namath s. Hussain, M.D. Penn state Hershey neurosurgery

Disclosures None

Background Several studies have shown that maximal tumor resection is associated with improved survival. Language and motor deficits in patients following brain tumor resection are frequently observed. A fundamental goal of neurosurgical management of brain tumors is to balance the extent of tumor resection (EOR) with the preservation of neurological function. Preoperative and intraoperative imaging techniques have been developed to improve the delineation of normal versus pathologic brain tissue and functional mapping of brain areas. Even with pre-surgical planning using functional MRI and diffusion tensor imaging (DTI), there can be new post-surgical functional deficits.

Diffusion Tensor Imaging DTI is an MRI technique the allows for the identification of subcortical white matter tracts. Exploits the random Brownian motion of water molecules in the brain to measure microstructural characteristics of tissue. In white matter, water diffusion is restricted by cellular barriers and exhibits ANISOTROPY (directionality) that is parallel to these axonal fibers. In CSF, water diffusion is not restricted. There is diffusion in all directions, exhibiting ISOTROPY.

Diffusion Tensor Imaging DTI uses spatial gradients in MRI to measure anisotropy and water diffusion, allowing the visualization of white matter tracts. DTI applications in neurosurgery: Preoperative diagnosis Tumor grading Intraoperative neuronavigation Prognosis for postoperative outcomes

Diffusion Tensor Imaging Studies have shown that incorporating DTI into preoperative imaging protocols can decrease postoperative deficits rates from 33% to 18% with 43% reduction in mortality. DTI shows strong concordance to intraoperative subcortical stimulation mapping during awake craniotomies (gold standard for mapping eloquent white matter). DTI has high sensitivity and specificity for detection of language and motor tracts (double of traditional fMRI). EOR has been shown to be improved from 77% with only electrical stimulation to 90% when DTI was integrated in neuronavigation.

Background No study has explored the prognostic value of the distance between the tumor and important subcortical white matter tracts or LTD (lesion to tract distance). The objective of this study was to correlate the distance of the surgical lesion to language and motor white-matter pathways and investigate its relationship to post-surgical functional deficits.

White Matters Tracts LTD measurements were taken to respect to the superior longitudinal fasciculus (SLF) and corticospinal tracts (CST).

Methods Adult patients with brain tumors (n=60) underwent pre-operative DTI scanning. Weakness and aphasia were recorded through standard preoperative and postoperative neurological exams. The major language and motor white matter pathways (left and right superior longitudinal fasciculi SLF, cingulum, and cortico-spinal tract CST) were identified from the DTI images and their lesion-to-tract distance (LTD) measured. Post-surgical morbidity and mortality information for each of the included patients were collected from their medical records.

Methods Images were acquired with GE 1.5T and 3T scanners. Axial DTI data was processed and reformatted for measuring LTD. Tumors margins were defined as the enhancing margin for tumors that enhance, and as the peripheral margin of solid T2 signal in nonenhancing tumors. Fractional anisotropy was used to define tract borders and overlaid onto structural MRI images.

Statistics ANOVA and Kruskal Wallis tests were used to determine differences in interval variables like age. Chi square and Fischer exact tests were used to determine if categorical variables differed between the groups. Kaplan-Meier survival analysis was performed along with log-rank testing to compare the relationship between LTD and survival. SPSS for all calculations. Significance values of p < 0.05 (2-sided) used.

Results

Results SLF, age was significantly different based on LTD

Results 1cm: 50% 2cm: 85% 1cm: 56% 2cm: 65%

Results SLF significantly associated with postoperative language deficits (p < 0.001) 74% with LTD < 1 cm had deficits 31% with LTD 1 – 2 cm 10% with LTD > 2 cm CST significantly associated with postoperative motor deficits (p = 0.018) 46% with LTD < 1 cm had deficits 11% with LTD 1 – 2 cm 8% with LTD > 2 cm Cingulum distance not associated with deficits (p = 0.255)

Results The LTD for ipsilesional CST and left-sided SLF was significantly associated with the occurrence rate of total and new functional motor and language deficits respectively. The LTD threshold that best predicted the occurrence of new deficits was found to be 1 cm (p<0.001). New deficit, LTD = 0.7 cm No deficits, LTD = 2.3 cm

Results Univariate logistic regression – no dependency between new language deficits and tumor size, grade. Cox regression analysis showed that age (p = 0.002) and presence of high grade tumor (p < 0.001) were predictive of mortality.

Results Kaplan-Meier log-rank survival analysis in patients having high- grade tumors demonstrated a significantly higher mortality for patients with an LTD for left-sided SLF smaller than 1 cm. No significant difference in survival due to LTD for cingulum (p = 0.873) or CST (p = 0.910).

Summary Our results suggest that a distance of 1 cm or greater from eloquent white matter structures is indicated to avoid new deficits with current surgical and imaging techniques. Our data indicates that adding DTI to pre-surgical planning can increase the predictive value for morbidity and mortality substantially.

Acknowledgements V. Prabhakaran W. Gaggl E. Meyer D. Huss B. Gilloon B. Swan M. Greenstein J. Voss R. Holdsworth C. Moritz V. A. Nair M.E. Meyerland J. Kuo M. K. Baskaya A. S. Field