Characterizing the relationship between fMRI derived measures and clinical outcomes in vascular lesion patients

Background and Purpose—Functional magnetic resonance imaging (fMRI) has proven to be an effective component of pretreatment planning in patients harboring a variety of different brain lesions. Our group has recently reported significant relationships concerning distances between brain tumor border and area of functional activation (Lesion-to-Activation-Distance; LAD) with regard to patient morbidity and mortality. This study further examines the relationship between LAD, focusing on a host of vascular lesions, and preand posttreatment morbidity. Materials and Methods—This study included a sample population (n=106) of patients with vascular lesions, primarily arteriovenous malformations (AVM) and cavernomas. These patients underwent pretreatment fMRI-based motor mapping (n=72) or language mapping (n=84). The impact of LAD and other variables derived from the patient medical record were analyzed with respect to functional deficits in terms of morbidity (weakness and/or aphasia). Results—In patients with no pretreatment deficits, there was trend for a significant relationship between Wernicke's area LAD and posttreatment language deficits. In patients with or without pretreatment deficits, a trend toward significance was observed between sensorimotor LAD and posttreatment motor deficits. Additionally, lesion type (AVMs or cavernomas) impacted posttreatment deficits with more patients with cavernomas showing posttreatment language deficits than patients with AVMs. This difference was however not observed for posttreatment motor deficits. Conclusion—These findings suggest that the proximity of a vascular lesion to sensorimotor and language areas is a relevant parameter in estimating patient prognosis in the peri-operative period. Additionally, vascular lesion type and existence of pretreatment deficits play a significant role in outcomes. Address Correspondence to: Vivek Prabhakaran, M.D., Ph.D. University of Wisconsin School of Medicine and Public Health Department of Radiology 600 Highland Avenue Madison, WI 53792-3252 Phone: 608-265-5269 Fax: 608-265-4152 vprabhakaran@uwhealth.org. NIH Public Access Author Manuscript Neurosurg Focus. Author manuscript; available in PMC 2013 October 25. Published in final edited form as: Neurosurg Focus. 2013 April ; 34(4): . doi:10.3171/2013.2.FOCUS12417. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript INTRODUCTION Blood oxygen level dependent functional MRI (BOLD-fMRI)11,12 has gained acceptance as an effective, noninvasive method of brain mapping for pretreatment planning.13 In particular, it has been demonstrated to be an effective means to establish language hemisphere dominance2,15,22 and its rendering of functional anatomy has correlated well with direct cortical stimulation mapping.3,8,14,21 For patients about to undergo treatment for various vascular brain lesions, however, fMRI presents unique challenges to the investigator.7,18 Radiologic examination of eloquent cortex utilizing principles of BOLD contrast in the vicinity of a lesion such as an AVM that features abnormal blood flow requires scrutiny of the reliability of activation and overall interpretation of results. Further, given the sensitivity of echo planar imaging to areas of parenchymal hemosiderin staining, vascular brain lesions such as cavernomas with previous hemorrhage may feature accelerated T2 shortening and T2* susceptibility effects that could compromise or render the regional BOLD signal unattainable. Thickbroom et al18 determined that flow related effects were less important than susceptibility artifact from hemosiderin staining, as the latter could contribute to possible underestimation of the extent of true activation. However, Lehericy et al7 suggested that AVMs resulting in severe flow anomalies could potentially compromise the reliability of BOLD signal in a region of interest. The importance of delineating areas of eloquent cortex remains an important goal for both clinicians and neuroradiologists. The compromise of eloquent areas as determined either by localizing the clinical deficits or based on conventional imaging has significant implications for treatment and prognosis. Specific grading schemes for arteriovenous malformations such as the widely used Spetzler-Martin criteria17 classically take into account AVM nidus measurement, location, and organization of venous drainage (See Table 1). Recently, additional prognostic characteristics of AVMs have been added to this list that have been termed angioarchitectual weakpoints.6 These weakpoints may confer greater propensity for hemorrhage and post-treatment risks including presence of nidal aneurysm, venous stenosis or ectasia, deep venous drainage, isolated or single venous drainage, and posterior fossa location. While some of these features are not specifically included in the classic SpetzlerMartin grading, it is important to consider these variables because of their prognostic value and impact on treatment strategies. For example, nidal aneurysms, particularly those exceeding 5 mm, may be treated with coil-embolization prior to surgical resection of the AVM. Further, identification and preservation of en passant arteries that might supply normal brain as well as an AVM is an important task. Currently, the imaging examinations in conjunction with clinical examination provide the diagnostic basis for a vascular lesion such as an AVM or cavernoma. There is a paucity of literature describing the utility of fMRI in routine pretreatment assessment of patients with vascular lesions. fMRI has been shown to be a robust technique for establishing language hemisphere dominance as well as useful for identification of eloquent cortex to be spared during surgery. However, its role in the special context of a vascular lesion is yet to be determined. This situation is further complicated by the fact that vascular lesion patients, including those examined prior to clinical intervention, may have atypical language networks.19 In the present study we investigate fMRI lesion-to-activation distance (LAD) and its relationship to morbidity in patients with vascular brain lesions about to undergo treatment, primarily AVMs and cavernomas. We hypothesize that as the LAD decreases, overall morbidity will increase. Gallagher et al. Page 2 Neurosurg Focus. Author manuscript; available in PMC 2013 October 25. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript MATERIALS AND METHODS Subject Characteristics This study was reviewed and approved by the University of Wisconsin–Madison Health Sciences Institutional Review Board (IRB). The sample population of (n=106) patients underwent pretreatment fMRI between June 1999 and July 2011 for various vascular brain lesions including AVMs and cavernomas. Demographic information is presented in Table 2. Patients gave informed consent in accordance with the study protocol approved by the IRB. Patients’ clinical information was extracted from the electronic medical record. Any record of pretreatment or posttreatment motor weakness (e.g., upper extremity, lower extremity, or facial weakness) or aphasia (e.g., Broca's type, Wernicke's type, conduction, or global aphasia) was included in the analysis. Only gross motor and language deficits were considered and no specific neuropsychological testing was included. Vascular lesions were diagnosed with catheter cerebral angiography, conventional CTA, or MRI/MRA imaging. Lesions were categorized as encroaching on sensorimotor cortex or primary language centers (i.e., Broca's area or Wernicke's area). Functional paradigms were selected depending upon the vascular lesion location in question with the aim of eliciting either primary sensorimotor or language center activation.9 fMRI activations were individually thresholded at the time of the radiologic examination in question and then made available for clinical use and decision-making; these same thresholded maps were used retrospectively in this study for distance measurements to characterize the prognostic utility of measures derived from these clinical fMRI maps. Given the wide variation in appearance and distribution of many vascular lesions, distance to the closest presumed edge of a vascular nidus was utilized. If a compact vascular nidus could not be definitively identified, distance to closest involved component of the vascular lesion was utilized. Distances from vascular lesion edge to the periphery of fMRI activation and distances from vascular lesion edge to the center of maximum primary motor or language fMRI activation were both measured. Distances were then correlated with preand posttreatment morbidity information obtained from the electronic medical record. fMRI Language Paradigms The language paradigms used to assess patients are described in more detail in Moritz et al.9 In brief, activation of Broca's area was best seen with word generation fMRI tasks. Two word generation tasks were used: (1) alternating 20-second blocks of antonym word generation and rest, and (2) alternating 20-second blocks of letter word generation task and rest. In the antonym word generation the subject is asked to silently think of the opposite of the word displayed on the screen. In the letter word generation task, the subject is asked to silently think of words starting with the letter displayed on the screen. Wernicke's area was identified with alternating 20-second blocks of text reading and symbols task. In this task, the patient silently read a short paragraph in the text reading block. During the control block, the patient was shown a paragraph of symbols and asked to scan for specific symbols within the paragraph. The control block controlled for eye movements during reading, which helped discriminate visual and eye movement-related activity from the true language areas. Not all patients performed all tasks. Tasks were individualized to the patient so that clinically useful and robust langua