Interobserver Variation in Cerebellar Tonsillar Tip Localization: Comparison of 3 Different Osseous Landmarks on Magnetic Resonance Imaging.

PURPOSE: The aim was to evaluate the interobserver agreement in the assessment of cerebellar tonsil position on sagittal magnetic resonance imaging using 3 different osseous landmarks. MATERIALS AND METHODS: This retrospective study consisted of brain magnetic resonance imagings performed at our institution in patients with and without Chiari I malformation between January 2010 and 2012. Sagittal T1-weighted images were reviewed by 2 senior board-certified neuroradiologists (blinded to underlying clinical diagnosis) with measurement of both cerebellar tonsillar positions based on lines drawn perpendicular from the tonsillar tip to the foramen magnum [FM] line, C1 line, and C2 line. Spearman correlation coefficients were calculated. Interobserver variation between the readers was assessed using Bland-Altman analysis and intraclass correlation coefficient. RESULTS: A total of 320 cerebellar tonsils on 160 patients, 50 with Chiari I malformations, and 110 control subjects without Chiari I malformation were evaluated. The Spearman correlation coefficients for the entire cohort were 0.86 (FM), 0.94 (C1), and 0.90 (C2). Bland-Altman analysis for the entire cohort showed the best interobserver agreement for C1 line (-0.3 mm bias) and the least for C2 line (4.6 mm bias). The Intraclass correlation coefficients for all patients were 0.84 (FM), 0.92 (C1), and 0.54 (C2). The least bias and highest correlation coefficients were also seen individually in the Chiari and non-Chiari cohorts with the C1 technique. CONCLUSIONS: Determination of cerebellar tonsillar position using a C1 arch landmark may be superior to the currently more commonly used FM-based landmark with lesser interobserver variability and higher interobserver correlation.

Seizure outcomes and mesial resection volumes following selective amygdalohippocampectomy and temporal lobectomy.

OBJECT: Anterior temporal lobectomy (ATL) and selective amygdalohippocampectomy (SelAH) are the preferred surgical approaches for the treatment of medically refractory epilepsy involving the nondominant and dominant temporal lobes, respectively. Both techniques provide access to mesial structures-with the ATL providing a wider surgical corridor than SelAH. Because the extent of mesial temporal resection potentially impacts seizure outcome, the authors examined mesial resection volumes, seizure outcomes, and neuropsychiatric test scores in patients undergoing either ATL or transcortical SelAH at a single institution. METHODS: A retrospective study was conducted in 96 patients with medically refractory mesial temporal lobe epilepsy. Fifty-one patients who had nondominant temporal lobe epilepsy underwent standard ATL, and 45 patients with language-dominant temporal lobe epilepsy underwent transcortical SelAH. Volumetric MRI analysis was used to quantify the mesial resection in both groups. In addition, the authors examined seizure outcomes and the change in neuropsychiatric test scores. RESULTS: Seizure-free outcome in the entire patient cohort was 94% at a mean follow-up of 44 months. There was no significant difference in the seizure outcome between the 2 groups. The extent of resection of the mesial structures following ATL was slightly higher than for SelAH (98% vs. 91%, p < 0.0001). The change in neuropsychiatric test scores largely reflected the side of surgery, but overall IQ and memory function did not change significantly in either group. CONCLUSIONS: Transcortical SelAH provides adequate access to the mesial structures, and allows for a resection that is nearly as extensive as that achieved with standard ATL. Seizure outcomes and neuropsychiatric sequelae are similar in both procedures.

Association Between Follow-Up Magnetic Resonance Imaging and Clinical Status Among Patients With Spinal Infections.

BACKGROUND: Spinal infections, including paraspinal and/or epidural abscesses and vertebral discitis and osteomyelitis, can have devastating consequences. The diagnostic imaging modality of choice has traditionally been magnetic resonance imaging (MRI) given the very high sensitivity and specificity, although the role of MRI in follow-up of spinal infections and how this relates to follow-up clinical status is poorly understood. We sought to understand the relationship between follow-up MRI and clinical status. METHODS: We conducted a retrospective review of adults with spinal infection to assess the relationship between follow-up MRI and clinical course. The degree of agreement between MRI and clinical follow-up was assessed using the Cohen kappa coefficient. A multinomial logistic regression model was applied to assess the impact of covariates in affecting the clinical outcome and MRI at follow-up independently. RESULTS: Ninety-eight patients met inclusion criteria during a 13-year period. We observed a lack of correlation between clinical follow-up status and MRI (κ = 0.065, P = 0.322). The McNemar-Bowker test for symmetry revealed that this disagreement was asymmetric (P < 0.001). Notably, clinical worsening was never associated with an improved MRI, and clinical improvement was overall not predictive of MRI result and vice versa. CONCLUSIONS: Routine follow-up MRI does not seem to correlate with clinical follow-up among patients with spinal infections. The use of MRI without new clinical indications in routine follow-up testing should be interpreted with caution.

Imaging Surveillance of Gliomas: Role of Basic and Advanced Imaging Techniques.

It is essential to be aware of widely accepted criteria for grading of treatment response in both high-grade and low-grade gliomas. These criteria primarily take into account responses of measurable and nonmeasurable lesions on T2-weighted, fluid-attenuated inversion recovery, and postcontrast images to determine a final category of response for the patient. The additional role that other advanced imaging techniques, such as diffusion and perfusion imaging, can play in the surveillance of these tumors is discussed in this article.

Multiple sclerosis presenting as acute acquired comitant esotropia in a pediatric patient.

Acute acquired comitant esotropia (AACE) is a rare form of esotropia in the older pediatric population. Although the workup for pediatric AACE varies, patients often do not undergo lab testing and imaging, because the overwhelming majority of cases are idiopathic. We describe AACE as the presenting manifestation of multiple sclerosis in a pediatric patient. His only other finding was a horizontal jerk nystagmus isolated to end gaze. Magnetic resonance imaging revealed extensive demyelinating lesions, with a small thalamic lesion possibly accounting for his esotropia. Our case underscores the need for extensive diagnostic workup for any ophthalmic or neurologic findings or symptoms accompanying AACE.

Comparison of Voxel-Wise and Histogram Analyses of Glioma ADC Maps for Prediction of Early Therapeutic Change.

Noninvasive imaging methods are sought to objectively predict early response to therapy for high-grade glioma tumors. Quantitative metrics derived from diffusion-weighted imaging, such as apparent diffusion coefficient (ADC), have previously shown promise when used in combination with voxel-based analysis reflecting regional changes. The functional diffusion mapping (fDM) metric is hypothesized to be associated with volume of tumor exhibiting an increasing ADC owing to effective therapeutic action. In this work, the reference fDM-predicted survival (from previous study) for 3 weeks from treatment initiation (midtreatment) is compared to multiple histogram-based metrics using Kaplan-Meier estimator for 80 glioma patients stratified to responders and nonresponders based on the population median value for the given metric. The ADC histogram metric reflecting reduction in midtreatment volume of solid tumor (ADC < 1.25 × 10-3 mm2/s) by >8% population-median with respect to pretreatment is found to have the same predictive power as the reference fDM of increasing midtreatment ADC volume above 4%. This study establishes the level of correlation between fDM increase and low-ADC tumor volume shrinkage for prediction of early response to radiation therapy in patients with glioma malignancies.

Predicting outcome of patients with high-grade gliomas after radiotherapy using quantitative analysis of T1-weighted magnetic resonance imaging.

PURPOSE: The aim of this study was to test the hypothesis that measuring quantitative changes in signal intensity early after radiotherapy (RT) in the contrast-enhancing tumor rim and nonenhancing core may be a noninvasive marker of early treatment response in patients with high-grade gliomas. METHODS AND MATERIALS: Twenty patients with high-grade gliomas had magnetic resonance imaging (MRI) performed 1 week before RT, during Weeks 1 and 3 of RT, and every 1 to 3 months after RT as part of a clinical prospective study. Regions of interest (ROI) including contrast-enhancing rim, and the nonenhancing core were defined automatically based on a calculated image of post- to precontrast T1-weighted MRI. Pretreatment T1-weighted MRI signal intensity changes were compared with Weeks 1 and 3 RT and 1 and 3 months post-RT MRI. Clinical and MRI parameters were then tested for prediction of overall survival. RESULTS: Regional T1-weighted signal intensity changes in both the contrast-enhancing rim and the nonenhancing core were observed in all patients during Week 1 and Week 3 of RT. Imaging parameters including signal intensity change within the nonenhancing core after Weeks 1 to 2 RT (p = 0.004), Weeks 3 to 4 RT (p = 0.002) and 1 month after completion of RT (p = 0.002) were predictive of overall survival. Using multivariate analysis including RTOG recursive partitioning analysis (RPA) and signal intensity change, only the signal intensity change in the nonenhancing core at 1 month after RT (p = 0.01) retained significance. CONCLUSION: Quantitative measurements of T1-weighted MRI signal intensity changes in the nonenhancing tumor core (using ratios of pre-post values) may provide valuable information regarding early response during treatment and improve our ability to predict posttreatment outcome.

Patient-Centered Assessment of the Value of Oral Contrast Material.

PURPOSE: The aim of this study was to measure the value of oral contrast material from the patient's point of view. METHODS: A prospective HIPAA-compliant survey was administered from August 30, 2016, to March 9, 2017, at two outpatient centers to consecutive outpatients immediately after oral contrast material consumption for abdominopelvic CT. The survey included validated measures of temporary health disutility and oral contrast-specific questions vetted by patient advocates with experience in survey design. Descriptive statistics were calculated. RESULTS: The response rate (93% [218 of 234]) and completion rate (100% [218 of 218]) were excellent. When given a hypothetical choice to not drink oral contrast, most subjects (89% [193 of 218]) stated that they would always drink it for fear of missing an important finding, and only 5 (2%) stated that they would never drink it regardless of risk. Twenty (9%) said that the decision to drink oral contrast would depend on the level of risk, with 18 (8%) indicating that they would accept a 0.01% to 1.00% risk for missing an important finding if they did not have to drink oral contrast. Most patients rated the oral contrast taste as tolerable (55% [120 of 218]); a minority rated it bad or terrible (10% [21 or 218]). Thirty-six subjects (17%) experienced concern or unease (8 minimal, 15 mild, 10 moderate, 3 extreme) when they learned that they had to drink oral contrast, and 36 (17%) experienced oral contrast-induced nausea or abdominal discomfort (10 minimal, 15 mild, 10 moderate, 1 extreme). CONCLUSIONS: If oral contrast material has any diagnostic benefit, most outpatients (89%) would rather drink it than accept any risk for missing an important finding.

BDNF Val66Met allele is associated with reduced hippocampal volume in healthy subjects.

BACKGROUND: A frequent polymorphism of the brain-derived neurotrophic factor (BDNF) gene (val(66)met) has been suggested to modulate hippocampal neuronal plasticity and has been associated with individual variations in emotional reactivity traits and episodic memory. METHODS: The hippocampal formation was outlined in high-resolution anatomical magnetic resonance imaging (MRI) data in a sample of 36 healthy volunteers and compared between individuals as a function of the presence of the met-BDNF allele. Both whole-brain volume corrected and uncorrected data were tested for effects of genotype, sex, and age. RESULTS: The met-BDNF allele was associated with an 11% reduction in the volume of the hippocampal formation. CONCLUSIONS: In spite of a relatively small sample size, the presence of the met-BDNF allele was found associated with a reduced volume of the hippocampal formation in healthy volunteers and may represent a vulnerability factor for the development of disease processes associated with the dysfunction of this brain region.

Evaluating changes in tumor volume using magnetic resonance imaging during the course of radiotherapy treatment of high-grade gliomas: Implications for conformal dose-escalation studies.

OBJECTIVE: To determine whether changes in tumor volume occur during the course of conformal 3D radiotherapy of high-grade gliomas by use of magnetic resonance imaging (MRI) during treatment and whether these changes had an impact on tumor coverage. METHODS AND MATERIALS: Between December 2000 and January 2004, 21 patients with WHO Grades 3 to 4 supratentorial malignant gliomas treated with 3D conformal radiotherapy (median dose, 70 Gy) were enrolled in a prospective clinical study. All patients underwent T1-weighted contrast-enhancing and T2-weighted and fluid-attenuated inversion recovery (FLAIR) imaging at approximately 1 to 2 weeks before radiotherapy, during radiotherapy (Weeks 1 and 3), and at routine intervals thereafter. All MRI scans were coregistered to the treatment-planning CT. Gross tumor volume (GTV Pre-Rx) was defined from a postoperative T1-weighted contrast-enhancing MRI performed 1 to 2 weeks before start of radiotherapy. A second GTV (GTV Week 3) was defined by use of an MRI performed during Week 3 of radiotherapy. A uniform 0.5 cm expansion of the respective GTV, PTV (Pre-Rx), and PTV (Week 3) was applied to the final boost plan. Dose-volume histograms (DVH) were used to analyze any potential adverse changes in tumor coverage based on Week 3 MRI. RESULTS: All MRI scans were reviewed independently by a neuroradiologist (DGH). Two patients were noted to have multifocal disease at presentation and were excluded from analysis. In 19 cases, changes in the GTV based on MRI at Week 3 during radiotherapy were as follows: 2 cases had an objective decrease in GTV (> or =50%); 12 cases revealed a slight decrease in the rim enhancement or changes in cystic appearance of the GTV; 2 cases showed no change in GTV; and 3 cases demonstrated an increase in tumor volume. Both cases with objective decreases in GTV during treatment were Grade 3 tumors. No cases of tumor progression were noted in Grade 3 tumors during treatment. In comparison, three of 12 Grade 4 tumors had tumor progression, based on MRI obtained during Week 3 of radiotherapy. Median increase in GTV (Week 3) was 11.7 cc (range, 9.8-21.3). Retrospective DVH analysis of PTV (Pre-Rx) and PTV (Week 3) demonstrated a decrease in V(95%)(PTV volume receiving 95% of the prescribed dose) in those 3 cases. CONCLUSIONS: Routine MR imaging during radiotherapy may be essential in ensuring tumor coverage if highly conformal radiotherapy techniques such as stereotactic boost and intensity-modulated radiotherapy are used in dose-escalation trials that utilize smaller treatment margins.

Improving cerebral cortical magnetic resonance imaging using a readily available surface coil.

Subtle structural deformities of the cerebral cortex have been shown to be the cause of seizures in patients with refractory epilepsy. Brain imaging using high-resolution focused protocols with standard head coils may not provide sufficient image quality needed for evaluating subtle cortical abnormalities. The authors describe the use of a readily available shoulder coil placed over a specific area of the brain that has been clinically determined to enhance the signal to noise and resolution of the cortical surface. Delineating the cortical surface using a shoulder coil can help to detect subtle areas of cortical thickening, blurring of the gray-white matter junction, or focally abnormal gyral and sulcal patterns.

A case study of unusual benign osseous lesion of the L5 lamina.

BACKGROUND: The differential diagnosis of benign-appearing posterior element lesions is complex. OBJECTIVE: To explore the etiology of an unusual benign lesion found on the lamina of L5 described in a case report. METHODS: Case report. The patient's medical, surgical and imaging histories as well as medical literature were reviewed. RESULTS: A 35-year old male complained of low back pain radiating to both legs for 5 months. Abdominal CT scan 1 year prior as well as post symptom-onset CT and MRI showed a well-corticated lesion lateral to the spinous process of L5. After failed rehabilitation and injection, operation revealed normal cortical bone. Pain was not markedly relieved post-operatively. CONCLUSION: The pre-surgical differential diagnosis of this lesion included osteosarcoma and osteoid osteoma, however benign pathological results suggest the possibility of atypical spina bifida occulta, Baastrup changes, atypical sacralization of L5, or a resolved fracture with heterotopic ossification.

Investigation of the diffusion abnormality index as a new imaging biomarker for early assessment of brain tumor response to radiation therapy.

BACKGROUND: Diffusion MRI, although having the potential to be a biomarker for early assessment of tumor response to therapy, could be confounded by edema and necrosis in or near the brain tumors. This study aimed to develop and investigate the ability of the diffusion abnormality index (DAI) to be a new imaging biomarker for early assessment of brain metastasis response to radiation therapy (RT). METHODS: Patients with either radiosensitive or radioresistant brain metastases that were treated by whole brain RT alone or combined with bortezomib as a radiation sensitizer had diffusion-weighted (DW) MRI pre-RT and 2 weeks (2W) after starting RT. A patient-specific diffusion abnormality probability function (DAProF) was created to account for abnormal low and high apparent diffusion coefficients differently, reflecting respective high cellularity and edema/necrosis. The DAI of a lesion was then calculated by the integral of DAProF-weighted tumor apparent diffusion coefficient histogram. The changes in DAI from pre-RT to 2W were evaluated for differentiating the responsive, stable, and progressive tumors and compared with the changes in gross tumor volume and conventional diffusion metrics during the same time interval. RESULTS: In lesions treated with whole brain RT, the DAI performed the best among all metrics in predicting the posttreatment response of brain metastases to RT. In lesions treated with whole brain RT + bortezomib, although DAI was the best predictor, the performance of all metrics worsened compared with the first group. CONCLUSIONS: The ability of DAI for early assessment of brain metastasis response to RT depends upon treatment regimes.

Physiological imaging-defined, response-driven subvolumes of a tumor.

PURPOSE: To develop an image analysis framework to delineate the physiological imaging-defined subvolumes of a tumor in relating to treatment response and outcome. METHODS AND MATERIALS: Our proposed approach delineates the subvolumes of a tumor based on its heterogeneous distributions of physiological imaging parameters. The method assigns each voxel a probabilistic membership function belonging to the physiological parameter classes defined in a sample of tumors, and then calculates the related subvolumes in each tumor. We applied our approach to regional cerebral blood volume (rCBV) and Gd-DTPA transfer constant (K(trans)) images of patients who had brain metastases and were treated by whole-brain radiation therapy (WBRT). A total of 45 lesions were included in the analysis. Changes in the rCBV (or K(trans))-defined subvolumes of the tumors from pre-RT to 2 weeks after the start of WBRT (2W) were evaluated for differentiation of responsive, stable, and progressive tumors using the Mann-Whitney U test. Performance of the newly developed metrics for predicting tumor response to WBRT was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: The percentage decrease in the high-CBV-defined subvolumes of the tumors from pre-RT to 2W was significantly greater in the group of responsive tumors than in the group of stable and progressive tumors (P<.007). The change in the high-CBV-defined subvolumes of the tumors from pre-RT to 2W was a predictor for post-RT response significantly better than change in the gross tumor volume observed during the same time interval (P=.012), suggesting that the physiological change occurs before the volumetric change. Also, K(trans) did not add significant discriminatory information for assessing response with respect to rCBV. CONCLUSION: The physiological imaging-defined subvolumes of the tumors delineated by our method could be candidates for boost target, for which further development and evaluation is warranted.

Concurrent temozolomide and dose-escalated intensity-modulated radiation therapy in newly diagnosed glioblastoma.

PURPOSE: To determine the maximum-tolerated dose (MTD) of radiation (RT) with concurrent temozolomide in patients with newly diagnosed glioblastoma (GBM), to estimate their progression-free (PFS) and overall survival (OS), and to assess the role of (11)C methionine PET (MET-PET) imaging in predicting recurrence. EXPERIMENTAL DESIGN: Intensity-modulated RT (IMRT) doses of 66 to 81 Gy, assigned to patients by the time-to-event continual reassessment method, were delivered over 6 weeks with concurrent daily temozolomide (75 mg/m(2)) followed by adjuvant cyclic temozolomide (200 mg/m(2) d1-5 q28d ×6 cycles). Treatment was based on gadolinium-enhanced MRI. Pretreatment MET-PET scans were obtained for correlation with eventual sites of failure. RESULTS: A total of 38 patients were analyzed with a median follow-up of 54 months for patients who remain alive. Late CNS grade ≥III toxicity was observed at 78 (2 of 7 patients) and 81 Gy (1 of 9 patients). None of 22 patients receiving 75 or less Gy developed RT necrosis. Median OS and PFS were 20.1 (14.0-32.5) and 9.0 (6.0-11.7) months, respectively. Twenty-two of 32 patients with pretreatment MET-PET uptake showed uptake beyond the contrast-enhanced MRI. Patients whose treatment did not include the region of increased MET-PET uptake showed an increased risk of noncentral failure (P < 0.001). CONCLUSIONS: Patients with GBM can safely receive standard temozolomide with 75 Gy in 30 fractions, delivered using IMRT. The median OS of 20.1 months is promising. Furthermore, MET-PET appears to predict regions of high risk of recurrence not defined by MRI, suggesting that further improvements may be possible by targeting metabolically active regions.

Association of 11C-methionine PET uptake with site of failure after concurrent temozolomide and radiation for primary glioblastoma multiforme.

PURPOSE: To determine whether increased uptake on 11C-methionine-PET (MET-PET) imaging obtained before radiation therapy and temozolomide is associated with the site of subsequent failure in newly diagnosed glioblastoma multiforme (GBM). METHODS: Patients with primary GBM were treated on a prospective trial with dose- escalated radiation and concurrent temozolomide. As part of the study, MET-PET was obtained before treatment but was not used for target volume definition. Using automated image registration, we assessed whether the area of increased MET-PET activity (PET gross target volume [GTV]) was fully encompassed within the high-dose region and compared the patterns of failure for those with and without adequate high-dose coverage of the PET-GTV. RESULTS: Twenty-six patients were evaluated with a median follow-up of 15 months. Nineteen of 26 had appreciable (>1 cm(3)) volumes of increased MET-PET activity before treatment. Five of 19 patients had PET-GTV that was not fully encompassed within the high-dose region, and all five patients had noncentral failures. Among the 14 patients with adequately covered PET-GTV, only two had noncentral treatment failures. Three of 14 patients had no evidence of recurrence more than 1 year after radiation therapy. Inadequate PET-GTV coverage was associated with increased risk of noncentral failures. (p < 0.01). CONCLUSION: Pretreatment MET-PET appears to identify areas at highest risk for recurrence for patients with GBM. It would be reasonable to test a strategy of incorporating MET-PET into radiation treatment planning, particularly for identifying areas for conformal boost.

Pitfalls in the diagnosis of mitochondrial encephalopathy with lactic acidosis and stroke-like episodes.

We describe a patient with genetically- and biochemically-proven mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) who was initially misdiagnosed as having had multiple ischemic strokes in part because the clinical presentation appeared to be acute, the MRI of lesions showed restricted diffusion, and the brain biopsy showed features suggestive of stroke. This report emphasizes the pitfalls in the diagnosis of MELAS and points out the similarities and differences between MELAS and ischemic stroke.

Sodium methohexital (brevital) as an anesthetic in the Wada test.

PURPOSES: We report our experience with sodium methohexital (Brevital) as an anesthetic used in the Wada test for language and memory in 86 epilepsy surgery patients (173 procedures). METHODS: The methods are compared with those of the more commonly used anesthetic sodium amobarbital (Amytal). RESULTS: Despite differences between the methohexital and amobarbital test protocols, the behavioral and neurologic effects of the two anesthetics are similar. Because of the brief duration of methohexital, two successive injections are made on each side rather than one, to lengthen the time available for testing both language and memory. Behavioral and EEG indices return to baseline more quickly and more completely with methohexital than with amobarbital, allowing several repetitions of the procedure without incremental drowsiness, and the total time taken for the procedure is less with methohexital than with amobarbital. CONCLUSIONS: The results of language and memory testing in the Wada test are equivalent for amobarbital and methohexital, except that methohexital has a briefer duration of action and is associated with less sedation.

Clinical applications of diffusion tensor imaging.

Directionally-ordered cellular structures that impede water motion, such as cell membranes and myelin, result in water mobility that is also directionally-dependent. Diffusion tensor imaging characterizes this directional nature of water motion and thereby provides structural information that cannot be obtained by standard anatomic imaging. Quantitative apparent diffusion coefficients and fractional anisotropy have emerged from being primarily research tools to methods enabling valuable clinical applications. This review describes the clinical utility of diffusion tensor imaging, including the basic principles of the technique, acquisition, data analysis, and the major clinical applications.