Detecting Primary Progressive Aphasia Atrophy Patterns: A Comparison of Visual Assessment and Quantitative Neuroimaging Techniques.

Background: There are now clinically available automated MRI analysis software programs that compare brain volumes of patients to a normative sample and provide z-score data for various brain regions. These programs have yet to be validated in primary progressive aphasia (PPA). Objective: To address this gap in the literature, we examined Neuroreader™ z-scores in PPA, relative to visual MRI assessment. We predicted that Neuroreader™ 1) would be more sensitive for detecting left > right atrophy in the cortical lobar regions in logopenic variant PPA clinical phenotype (lvPPA), and 2) would distinguish lvPPA (n = 11) from amnestic mild cognitive impairment (aMCI; n = 12). Methods: lvPPA or aMCI patients who underwent MRI with Neuroreader™ were included in this study. Two neuroradiologists rated 10 regions. Neuroreader™ lobar z-scores for those 10 regions, as well as a hippocampal asymmetry metric, were included in analyses. Results: Cohen's Kappa coefficients were significant in 10 of the 28 computations (k = 0.351 to 0.593, p≤0.029). Neuroradiologists agreed 0% of the time that left asymmetry was present across regions. No significant differences emerged between aMCI and lvPPA in Neuroreader™ z-scores across left or right frontal, temporal, or parietal regions (ps > 0.10). There were significantly lower z-scores in the left compared to right for the hippocampus, as well as parietal, occipital, and temporal cortices in lvPPA. Conclusion: Overall, our results indicated moderate to low interrater reliability, and raters never agreed that left asymmetry was present. While lower z-scores in the left hemisphere regions emerged in lvPPA, Neuroreader™ failed to differentiate lvPPA from aMCI.

Radiomic Features of Multiparametric MRI Present Stable Associations With Analogous Histological Features in Patients With Brain Cancer.

Magnetic resonance (MR)-derived radiomic features have shown substantial predictive utility in modeling different prognostic factors of glioblastoma and other brain cancers. However, the biological relationship underpinning these predictive models has been largely unstudied, and the generalizability of these models had been called into question. Here, we examine the localized relationship between MR-derived radiomic features and histology-derived "histomic" features using a data set of 16 patients with brain cancer. Tile-based radiomic features were collected on T1, post-contrast T1, FLAIR, and diffusion-weighted imaging (DWI)-derived apparent diffusion coefficient (ADC) images acquired before patient death, with analogous histomic features collected for autopsy samples coregistered to the magnetic resonance imaging. Features were collected for each original image, as well as a 3D wavelet decomposition of each image, resulting in 837 features per MR and histology image. Correlative analyses were used to assess the degree of association between radiomic-histomic pairs for each magnetic resonance imaging. The influence of several confounds was also assessed using linear mixed-effect models for the normalized radiomic-histomic distance, testing for main effects of different acquisition field strengths. Results as a whole were largely heterogeneous, but several features showed substantial associations with their histomic analogs, particularly those derived from the FLAIR and postcontrast T1W images. These features with the strongest association typically presented as stable across field strengths as well. These data suggest that a subset of radiomic features can consistently capture texture information on underlying tissue histology.

Diagnosis of spinal dural arteriovenous fistula using 3D T2-weighted imaging.

PURPOSE: To evaluate spinal MRIs without and with 3D T2W imaging among patients without and with spinal dural arteriovenous fistula (SDAVF) confirmed by spinal digital subtraction angiography (DSA). METHODS: A retrospective case-control study was performed among patients without and with SDAVF who had both spinal MRIs and gold standard spinal DSA. Two neuroradiologists independently reviewed spinal MRIs that were performed with either sagittal T2W turbo spin echo (2D group) or sagittal 3D T2W sampling perfection with application-optimized contrasts using different flip-angle evolutions (SPACE) (3D group) and documented the presence or absence of SDAVF. Using spinal DSA diagnosis as a gold standard, the sensitivity, specificity, and interobserver agreement for the 2D-group and 3D-group MRI diagnosis were calculated. RESULTS: The 2D group consisted of 21 patients and the 3D group consisted of 16 patients. For both radiologists, the 2D group demonstrated a sensitivity of 100% and specificity of 100%. Interobserver agreement in the 2D group was perfect (k = 1.0). For both radiologists, the 3D group demonstrated sensitivity of 100.0% and specificity of 92.3%. Interobserver agreement in the 3D group was perfect (k = 1.0). While flow voids were considered more conspicuous, spinal cord signal abnormality was considered less conspicuous with 3D T2W SPACE compared with conventional 2D STIR sequence. CONCLUSION: 3D T2W SPACE should be used in conjunction with 2D T2W sequences to more accurately detect abnormal cord signal and determine when perimedullary flow voids are pathologically abnormal for the radiologic diagnosis of SDAVF.

Prophylactic Anticonvulsants in Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Prophylactic anticonvulsants are routinely prescribed in the acute setting for intracerebral hemorrhage (ICH) patients, but some studies have reported an association with worse outcomes. We sought to characterize the prevalence and predictors of prophylactic anticonvulsant administration after ICH as well as guideline adherence. We also sought to determine whether prophylactic anticonvulsants were independently associated with poor outcome. METHODS: We performed a retrospective study of primary ICH in our two academic centers. We used a propensity matching approach to make treated and non-treated groups comparable. We conducted multiple logistic regression analysis to identify independent predictors of prophylactic anticonvulsant initiation and its association with poor outcome as measured by modified Rankin score. RESULTS: We identified 610 patients with primary ICH, of whom 98 were started on prophylactic anticonvulsants. Levetiracetam (97%) was most commonly prescribed. Age (OR 0.97, 95% CI 0.95-0.99, p < .001), lobar location (OR 2.94, 95% CI 1.76-4.91, p < .001), higher initial National Institutes of Health Stroke Scale (NIHSS) score (OR 2.31, 95% CI 1.40-3.79, p = .001), craniotomy (OR 3.06, 95% CI 1.51-6.20, p = .002), and prior ICH (OR 2.36, 95% CI 1.10-5.07, p = .028) were independently associated with prophylactic anticonvulsant initiation. Prophylactic anticonvulsant use was not associated with worse functional outcome [modified Rankin score (mRS) 4-6] at hospital discharge or with increased case-fatality. There was no difference in prescribing patterns after 2010 guideline publication. DISCUSSION: Levetiracetam was routinely prescribed following ICH and was not associated with worse outcomes. Future investigations should examine the effect of prophylactic levetiracetam on cost and neuropsychological outcomes as well as the role of continuous EEG in identifying subclinical seizures.

Disparities and guideline adherence in drugs of abuse screening in intracerebral hemorrhage.

OBJECTIVE: To characterize the pattern of urine drug screening in a cohort of intracerebral hemorrhage (ICH) patients at our academic centers. METHODS: We identified cases of primary ICH occurring from 2009 to 2011 in our academic centers. Demographic data, imaging characteristics, processes of care, and short-term outcomes were ascertained. We performed logistic regression to identify predictors for screening and evaluated preguideline and postguideline reiteration screening patterns. RESULTS: We identified 610 patients with primary ICH in 2009-2011; 379 (62.1%) were initially evaluated at an outside hospital. Overall, 142/610 (23.3%) patients were screened, with 21 positive for cocaine and 3 for amphetamine. Of patients <55 years of age, only 65/140 (46.4%) were screened. Black patients <55 years of age were screened more than nonblack patients <55 years of age (38/61 [62.3%] vs 27/79 [34.2%]; p = 0.0009). In the best multivariable model, age group (p = 0.0001), black race (p = 0.4529), first Glasgow Coma Scale score (p = 0.0492), current smoking (p < 0.0001), and age group × black race (p = 0.0097) were associated with screening. Guideline reiteration in 2010 did not improve the proportion <55 years of age who were screened: 42/74 (56.8%) were screened before and 23/66 (34.9%) after (p = 0.01). CONCLUSIONS: We found disparities in drugs of abuse (DOA) screening and suboptimal guideline adherence. Systematic efforts to improve screening for DOA are warranted. Improved identification of sympathomimetic exposure may improve etiologic classification and influence decision-making and prognosis counseling.

Cerebral Perfusion and Gray Matter Changes Associated With Chemotherapy-Induced Peripheral Neuropathy.

PURPOSE: To investigate the longitudinal relationship between chemotherapy-induced peripheral neuropathy (CIPN) symptoms (sx) and brain perfusion changes in patients with breast cancer. Interaction of CIPN-sx perfusion effects with known chemotherapy-associated gray matter density decrease was also assessed to elucidate the relationship between CIPN and previously reported cancer treatment-related brain structural changes. METHODS: Patients with breast cancer treated with (n = 24) or without (n = 23) chemotherapy underwent clinical examination and brain magnetic resonance imaging at the following three time points: before treatment (baseline), 1 month after treatment completion, and 1 year after the 1-month assessment. CIPN-sx were evaluated with the self-reported Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity four-item sensory-specific scale. Perfusion and gray matter density were assessed using voxel-based pulsed arterial spin labeling and morphometric analyses and tested for association with CIPN-sx in the patients who received chemotherapy. RESULTS: Patients who received chemotherapy reported significantly increased CIPN-sx from baseline to 1 month, with partial recovery by 1 year (P < .001). CIPN-sx increase from baseline to 1 month was significantly greater for patients who received chemotherapy compared with those who did not (P = .001). At 1 month, neuroimaging showed that for the group that received chemotherapy, CIPN-sx were positively associated with cerebral perfusion in the right superior frontal gyrus and cingulate gyrus, regions associated with pain processing (P < .001). Longitudinal magnetic resonance imaging analysis in the group receiving chemotherapy indicated that CIPN-sx and associated perfusion changes from baseline to 1 month were also positively correlated with gray matter density change (P < .005). CONCLUSION: Peripheral neuropathy symptoms after systemic chemotherapy for breast cancer are associated with changes in cerebral perfusion and gray matter. The specific mechanisms warrant further investigation given the potential diagnostic and therapeutic implications.

Altered cerebral blood flow one month after systemic chemotherapy for breast cancer: a prospective study using pulsed arterial spin labeling MRI perfusion.

Cerebral structural and functional alterations have been reported after chemotherapy for non-CNS cancers, yet the causative mechanism behind these changes remains unclear. This study employed a novel, non-invasive, MRI-based neuroimaging measure to provide the first direct longitudinal measurement of resting cerebral perfusion in breast cancer patients, which was tested for association with changes in cognitive function and gray matter density. Perfusion was measured using pulsed arterial spin labeling MRI in women with breast cancer treated with (N = 27) or without (N = 26) chemotherapy and matched healthy controls (N = 26) after surgery before other treatments (baseline), and one month after chemotherapy completion or yoked intervals. Voxel-based analysis was employed to assess perfusion in gray matter; changes were examined in relation to overall neuropsychological test performance and frontal gray matter density changes measured by structural MRI. Baseline perfusion was not significantly different across groups. Unlike control groups, chemotherapy-treated patients demonstrated significantly increased perfusion post-treatment relative to baseline, which was statistically significant relative to controls in the right precentral gyrus. This perfusion increase was negatively correlated with baseline overall neuropsychological performance, but was not associated with frontal gray matter density reduction. However, decreased frontal gray matter density was associated with decreased perfusion in bilateral frontal and parietal lobes in the chemotherapy-treated group. These findings indicate that chemotherapy is associated with alterations in cerebral perfusion which are both related to and independent of gray matter changes. This pattern of results suggests the involvement of multiple mechanisms of chemotherapy-induced cognitive dysfunction. Additionally, lower baseline cognitive function may be a risk factor for treatment-associated perfusion dysregulation. Future research is needed to clarify these mechanisms, identify individual differences in susceptibility to treatment-associated changes, and further examine perfusion change over time in survivors.

Altered default mode network connectivity in older adults with cognitive complaints and amnestic mild cognitive impairment.

Default mode network (DMN) disruption has been reported in Alzheimer's disease (AD), yet the specific pattern of altered connectivity over the course of prodromal AD remains to be characterized. The aim of this study was to assess DMN connectivity in older adults with informant-verified cognitive complaints (CC) but normal neuropsychological performance compared to individuals with mild cognitive impairment (MCI) and healthy controls (HC). DMN maps were derived from resting-state fMRI using independent component analysis. Group comparisons of DMN connectivity were performed between older adults with MCI (n = 18), CC (n = 23), and HC (n = 16). Both CC and MCI showed decreased DMN connectivity in the right hippocampus compared to HC, with the CC group showing greater connectivity than MCI. These differences survived atrophy correction and correlated with cognitive performance. DMN connectivity appears sensitive to early prodromal neurodegenerative changes associated with AD, notably including pre-MCI individuals with cognitive complaints.

Strategies to maximize resection of complex, or high surgical risk, low-grade gliomas.

OBJECT: Early and aggressive resection of low-grade gliomas (LGGs) leads to increased overall patient survival, decreased malignant progression, and better seizure control. This case series describes the authors' approach to achieving optimal neurological and surgical outcomes in patients referred by outside neurosurgeons for stereotactic biopsy of tumors believed to be complex or a high surgical risk, due to their diffuse nature on neuroimaging and their obvious infiltration of functional cortex. METHODS: Seven patients underwent individualized neuroimaging evaluation preoperatively, which included routine brain MRI with and without contrast administration for intraoperative neuronavigation, functional MRI with speech and motor mapping, diffusion tensor imaging to delineate white matter tracts, and MR perfusion to identify potential foci of higher grade malignancy within the tumor. Awake craniotomy with intraoperative motor and speech mapping was performed in all patients. Tumor removal was initiated through a transsylvian approach for insular lesions, and through multiple corticotomies in stimulation-confirmed noneloquent areas for all other lesions. Resection was continued until neuronavigation indicated normal brain, cortical or subcortical stimulation revealed functional cortex, or the patient began to experience a minor neurological deficit on intraoperative testing. RESULTS: Gross-total resection was achieved in 1 patient and subtotal resection (> 80%) in 6 patients, as assessed by postoperative MRI. Over the average follow-up duration of 31 months, no patient experienced a progression or recurrence. Long-term seizure control was excellent in 6 patients who achieved Engel Class I outcomes. Neurologically, all 7 patients experienced mild temporary deficits or seizures that completely resolved, and 1 patient continues to have mild expressive aphasia. CONCLUSIONS: Significant resection of diffuse, infiltrating LGGs is possible, even in presumed eloquent cortex. Aggressive resection maximizes seizure control and does not necessarily cause permanent neurological deficits. Individualized preoperative neuroimaging evaluation, including tractography and awake craniotomy with intraoperative speech and motor mapping, is an essential tool in achieving these outcomes.

Accuracy of CT cerebral perfusion in predicting infarct in the emergency department: lesion characterization on CT perfusion based on commercially available software.

This study aims to assess the diagnostic accuracy of a single vendor commercially available CT perfusion (CTP) software in predicting stroke. A retrospective analysis on patients presenting with stroke-like symptoms within 6 h with CTP and diffusion-weighted imaging (DWI) was performed. Lesion maps, which overlays areas of computer-detected abnormally elevated mean transit time (MTT) and decreased cerebral blood volume (CBV), were assessed from a commercially available software package and compared to qualitative interpretation of color maps. Using DWI as the gold standard, parameters of diagnostic accuracy were calculated. Point biserial correlation was performed to assess for relationship of lesion size to a true positive result. Sixty-five patients (41 females and 24 males, age range 22-92 years, mean 57) were included in the study. Twenty-two (34 %) had infarcts on DWI. Sensitivity (83 vs. 70 %), specificity (21 vs. 69 %), negative predictive value (77 vs. 84 %), and positive predictive value (29 vs. 50 %) for lesion maps were contrasted to qualitative interpretation of perfusion color maps, respectively. By using the lesion maps to exclude lesions detected qualitatively on color maps, specificity improved (80 %). Point biserial correlation for computer-generated lesions (R pb = 0.46, p < 0.0001) and lesions detected qualitatively (R pb = 0.32, p = 0.0016) demonstrated positive correlation between size and infarction. Seventy-three percent (p = 0.018) of lesions which demonstrated an increasing size from CBV, cerebral blood flow, to MTT/time to peak were true positive. Used in isolation, computer-generated lesion maps in CTP provide limited diagnostic utility in predicting infarct, due to their inherently low specificity. However, when used in conjunction with qualitative perfusion color map assessment, the lesion maps can help improve specificity.

Visual contrast sensitivity in Alzheimer's disease, mild cognitive impairment, and older adults with cognitive complaints.

Deficits in contrast sensitivity (CS) have been reported in Alzheimer's disease (AD). However, the extent of these deficits in prodromal AD stages, including mild cognitive impairment (MCI) or even earlier, has not been investigated. In this study, CS was assessed using frequency doubling technology in older adults with AD (n = 10), amnestic MCI (n = 28), cognitive complaints without performance deficits (CC; n = 20), and healthy controls (HC; n = 29). The association between CS and cognition was also evaluated. Finally, the accuracy of CS measures for classifying MCI versus HC was evaluated. CS deficits were found in AD and MCI, while CC showed intermediate performance between MCI and HC. Upper right visual field CS showed the most significant difference among groups. CS was also associated with cognitive performance. Finally, CS measures accurately classified MCI versus HC. The CS deficits in AD and MCI, and intermediate performance in CC, indicate that these measures are sensitive to early AD-associated changes. Therefore, frequency doubling technology-based measures of CS may have promise as a novel AD biomarker.