J M Mountz

University of Pittsburgh, Pittsburgh, Pennsylvania, United States

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Publications (143)577.73 Total impact

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    ABSTRACT: PurposeThis work intends to demonstrate a new method for quantifying concentration of sodium (23Na) of bi-exponential T2 relaxation in patients on MRI scanners at 3.0 Tesla.Theory and Methods Two single-quantum (SQ) sodium images acquired at very-short and short echo times (TE = 0.5 and 5.0 ms) are subtracted to produce an image of the short-T2 component of the bi-exponential (or bound) sodium. An integrated calibration on the SQ and short-T2 images quantifies both total and bound sodium concentrations. Numerical models were used to evaluate signal response of the proposed method to the short-T2 components. MRI scans on agar phantoms and brain tumor patients were performed to assess accuracy and performance of the proposed method, in comparison with a conventional method of triple-quantum filtering.ResultsA good linear relation (R2 = 0.98) was attained between the short-T2 image intensity and concentration of bound sodium. A reduced total scan time of 22 min was achieved under the SAR restriction for human studies in quantifying both total and bound sodium concentrations.Conclusion The proposed method is feasible for quantifying bound sodium concentration in routine clinical settings at 3.0 Tesla. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.
    Magnetic Resonance in Medicine 07/2014; · 3.27 Impact Factor
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    Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 05/2014;
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    ABSTRACT: The authors present the first use of the novel positron emission tomography (PET) apoptosis tracer (18)F-labeled 2-(5-fluoro-pentyl)-2-methyl-malonic acid ((18)F-ML-10) for early-therapy response assessment of a newly diagnosed glioblastoma multiforme (GBM) patient. A 71-year-old male with a newly diagnosed GBM received (18)F-ML-10 PET scans prior to therapy initiation (baseline) and after completing 3 weeks of whole-brain radiation therapy with concomitant temozolomide chemotherapy (early-therapy assessment, ETA). The baseline (18)F-ML-10 PET scan showed increased tracer uptake at the site of the GBM, with highest activity toward the central portion of the tumor. At the ETA time point, a new distribution of tracer uptake was observed compared to baseline. Normalized pixel-by-pixel subtraction of baseline from ETA was used to quantify change in tracer distribution between (18)F-ML-10 PET imaging time points. Results of this analysis showed reduction in (18)F-ML-10 uptake at the site of greatest baseline uptake, but increased uptake around the periphery of the tumor at the early-therapy time point. The changing patterns of (18)F-ML-10 uptake between baseline and ETA are suggestive for therapy-induced tumor cellular apoptosis.
    Brain and behavior. 03/2014; 4(2):312-5.
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    ABSTRACT: To evaluate the ability of various software (SW) tools used for quantitative image analysis to properly account for source-specific image scaling employed by magnetic resonance imaging manufacturers. A series of gadoteridol-doped distilled water solutions (0%, 0.5%, 1%, and 2% volume concentrations) was prepared for manual substitution into one (of three) phantom compartments to create "variable signal," whereas the other two compartments (containing mineral oil and 0.25% gadoteriol) were held unchanged. Pseudodynamic images were acquired over multiple series using four scanners such that the histogram of pixel intensities varied enough to provoke variable image scaling from series to series. Additional diffusion-weighted images were acquired of an ice-water phantom to generate scanner-specific apparent diffusion coefficient (ADC) maps. The resulting pseudodynamic images and ADC maps were analyzed by eight centers of the Quantitative Imaging Network using 16 different SW tools to measure compartment-specific region-of-interest intensity. Images generated by one of the scanners appeared to have additional intensity scaling that was not accounted for by the majority of tested quantitative image analysis SW tools. Incorrect image scaling leads to intensity measurement bias near 100%, compared to nonscaled images. Corrective actions for image scaling are suggested for manufacturers and quantitative imaging community.
    Translational oncology 02/2014; 7(1):65-71. · 3.40 Impact Factor
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    ABSTRACT: Pharmacokinetic analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) time-course data allows estimation of quantitative parameters such as K (trans) (rate constant for plasma/interstitium contrast agent transfer), v e (extravascular extracellular volume fraction), and v p (plasma volume fraction). A plethora of factors in DCE-MRI data acquisition and analysis can affect accuracy and precision of these parameters and, consequently, the utility of quantitative DCE-MRI for assessing therapy response. In this multicenter data analysis challenge, DCE-MRI data acquired at one center from 10 patients with breast cancer before and after the first cycle of neoadjuvant chemotherapy were shared and processed with 12 software tools based on the Tofts model (TM), extended TM, and Shutter-Speed model. Inputs of tumor region of interest definition, pre-contrast T1, and arterial input function were controlled to focus on the variations in parameter value and response prediction capability caused by differences in models and associated algorithms. Considerable parameter variations were observed with the within-subject coefficient of variation (wCV) values for K (trans) and v p being as high as 0.59 and 0.82, respectively. Parameter agreement improved when only algorithms based on the same model were compared, e.g., the K (trans) intraclass correlation coefficient increased to as high as 0.84. Agreement in parameter percentage change was much better than that in absolute parameter value, e.g., the pairwise concordance correlation coefficient improved from 0.047 (for K (trans)) to 0.92 (for K (trans) percentage change) in comparing two TM algorithms. Nearly all algorithms provided good to excellent (univariate logistic regression c-statistic value ranging from 0.8 to 1.0) early prediction of therapy response using the metrics of mean tumor K (trans) and k ep (=K (trans)/v e, intravasation rate constant) after the first therapy cycle and the corresponding percentage changes. The results suggest that the interalgorithm parameter variations are largely systematic, which are not likely to significantly affect the utility of DCE-MRI for assessment of therapy response.
    Translational oncology 02/2014; 7(1):153-66. · 3.40 Impact Factor
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    ABSTRACT: Evaluation of cancer-therapy efficacy at early time points is necessary for realizing the goal of delivering maximally effective treatment. Molecular imaging with carefully selected tracers and methodologies can provide the means for realizing this ability. Many therapies are aimed at inducing apoptosis in malignant tissue; thus, the ability to quantify apoptosis in vivo may be a fruitful approach. Apoptosis rate changes occur on a fast time scale, potentially allowing correspondingly rapid decisions regarding therapy value. However, quantification of tissue status based on apoptosis imaging is complicated by this time scale and by the spatial heterogeneity of the process. Using the positron emission tomography (PET) tracer 2-(5-fluoro-pentyl)-2-methyl-malonic acid (F-18 ML-10), we present methods of voxelwise analysis yielding quantitative measures of apoptosis changes, parametric apoptosis change images, and graphical representation of apoptotic features. A method of deformable registration to account for anatomic changes between scan time points is also demonstrated. Overall apoptotic rates deduced from imaging depend on tumor density and the specific rate of apoptosis, a situation resulting in an ambiguity in the source of observed image-based changes. The ambiguity may be resolved through multimodality imaging. An example of intracellular sodium magnetic resonance imaging coupled with F-18 ML-10 PET is provided.
    Translational oncology 02/2014; 7(1):111-9. · 3.40 Impact Factor
  • Gonca G Bural, Frank Lieberman, James M Mountz
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    ABSTRACT: A 57-year-old man with a history of multiple recurrent atypical meningiomas (World Health Organization grade II) had several surgical resections including γ knife resection of the parafalcine meningioma, followed with a stereotactic radiosurgical ablation. Despite these treatments, an MRI scan performed 7 months later showed progression of the disease. The patient remained symptomatic with intermittent severe headaches associated with nausea, vomiting, and visual disturbance. He had a positive In-pentetreotide indicating the presence of somatostatin receptors. Therefore, he was placed on systemic Sandostatin (octreotide acetate) treatment, and at follow-up, he was clinically responsive to treatment.
    Clinical nuclear medicine 01/2014; · 3.92 Impact Factor
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    ABSTRACT: Malignant gliomas consist of glioblastomas, anaplastic astrocytomas, anaplastic oligodendrogliomas and anaplastic oligoastrocytomas, and some less common tumors such as anaplastic ependymomas and anaplastic gangliogliomas. Malignant gliomas have high morbidity and mortality. Even with optimal treatment, median survival is only 12-15 months for glioblastomas and 2-5 years for anaplastic gliomas. However, recent advances in imaging and quantitative analysis of image data have led to earlier diagnosis of tumors and tumor response to therapy, providing oncologists with a greater time window for therapy management. In addition, improved understanding of tumor biology, genetics, and resistance mechanisms has enhanced surgical techniques, chemotherapy methods, and radiotherapy administration. After proper diagnosis and institution of appropriate therapy, there is now a vital need for quantitative methods that can sensitively detect malignant glioma response to therapy at early follow-up times, when changes in management of nonresponders can have its greatest effect. Currently, response is largely evaluated by measuring magnetic resonance contrast and size change, but this approach does not take into account the key biologic steps that precede tumor size reduction. Molecular imaging is ideally suited to measuring early response by quantifying cellular metabolism, proliferation, and apoptosis, activities altered early in treatment. We expect that successful integration of quantitative imaging biomarker assessment into the early phase of clinical trials could provide a novel approach for testing new therapies, and importantly, for facilitating patient management, sparing patients from weeks or months of toxicity and ineffective treatment. This review will present an overview of epidemiology, molecular pathogenesis and current advances in diagnoses, and management of malignant gliomas.
    Cancer Management and Research 01/2014; 6:149-170.
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    ABSTRACT: Intratumoral metabolic heterogeneity may increase the likelihood of treatment failure due to the presence of a subset of resistant tumor cells. Using a head and neck squamous cell carcinoma (HNSCC) xenograft model and a real-time fluorescence imaging approach, we tested the hypothesis that tumors are metabolically heterogeneous, and that tumor hypoxia alters patterns of glucose uptake within the tumor.
    PLoS ONE 01/2014; 9(8):e102452. · 3.73 Impact Factor
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    ABSTRACT: Early therapy response assessment in glioblastoma multiforme remains a challenge. Evaluation by MRI relies on changes in tumor contrast enhancement or size, which are usually not visible at early therapy response assessment times. In addition, MRI may not be reliable for early therapy response assessment if only molecular changes have occurred. PET with F-FLT, a tracer associated with cellular proliferation, has been proposed as a potential method of early therapy response assessment and is an area of active research. We present a case where early response assessment with F-FLT PET was associated with a favorable 1-year follow-up outcome.
    Clinical nuclear medicine 12/2013; · 3.92 Impact Factor
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    ABSTRACT: The ability to differentiate between brain tumor progression and radiation therapy induced necrosis is critical for appropriate patient management. In order to improve the differential diagnosis, we combined fluorine-18 2-fluoro-deoxyglucose positron emission tomography ((18)F-FDG PET), proton magnetic resonance spectroscopy ((1)H MRS) and histological data to develop a multi-parametric machine-learning model. We enrolled twelve post-therapy patients with grade 2 and 3 gliomas that were suspicious of tumor progression. All patients underwent (18)F-FDG PET and (1)H MRS. Maximal standardized uptake value (SUVmax) of the tumors and reference regions were obtained. Multiple 2D maps of choline (Cho), creatine (Cr), and N-acetylaspartate (NAA) of the tumors were generated. A support vector machine (SVM) learning model was established to take imaging biomarkers and histological data as input vectors. A combination of clinical follow-up and multiple sequential MRI studies served as the basis for assessing the clinical outcome. All vector combinations were evaluated for diagnostic accuracy and cross validation. The optimal cutoff value of individual parameters was calculated using Receiver operating characteristic (ROC) plots. The SVM and ROC analyses both demonstrated that SUVmax of the lesion was the most significant single diagnostic parameter (75% accuracy) followed by Cho concentration (67% accuracy). SVM analysis of all paired parameters showed SUVmax and Cho concentration in combination could achieve 83% accuracy. SUVmax of the lesion paired with SUVmax of the white matter as well as the tumor Cho paired with the tumor Cr both showed 83% accuracy. These were the most significant paired diagnostic parameters of either modality. Combining all four parameters did not improve the results. However, addition of two more parameters, Cho and Cr of brain parenchyma contralateral to the tumor, increased the accuracy to 92%. This study suggests that SVM models may improve detection of glioma progression more accurately than single parametric imaging methods. National Cancer Institute, Cancer Center Support Grant Supplement Award, Imaging Response Assessment Teams.
    European journal of radiology 11/2013; · 2.65 Impact Factor
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    ABSTRACT: Background: Pulmonary lesions from active tuberculosis patients are thought to contain persistent, nonreplicating bacilli that arise from hypoxic stress. Metronidazole, approved for anaerobic infections, has anti-tuberculosis activity against anoxic bacilli in vitro and in some animal models and may target persistent, nonreplicating bacilli.Methods: In this double-blind, placebo-controlled trial, pulmonary multidrug-resistant tuberculosis subjects were randomly assigned to receive metronidazole 500 mg thrice daily or placebo for 8 weeks in addition to an individualized background regimen. Outcomes were measured radiologically (change on high resolution computed tomography [HRCT]), microbiologically (time to sputum smear, culture conversion), and clinically (status 6 months after stopping therapy).Results: Enrollment was stopped early due to excessive peripheral neuropathies in the metronidazole arm. Among 35 subjects randomized, 31 (15 metronidazole, 16 placebo) were included in the modified intent-to-treat analysis. There were no significant differences by arm in improvement of HRCT lesions from baseline to 2 or 6 months. More subjects in the metronidazole arm converted their sputum smear (P=0.04) and liquid culture (P=0.04) to negative at 1 month but these differences were lost by 2 months. Overall, 81% were clinically successful six months after stopping therapy, with no differences by arm. However, 8/16 (50%) of subjects in the metronidazole group and 2/17 (12%) of those in the placebo group developed peripheral neuropathy. Subjects who received metronidazole were 4.3 fold (95% CI 1.1-17.1) more likely to develop peripheral neuropathies than subjects who received placebo.Conclusions: Metronidazole may have increased early sputum smear and culture conversion but was too neurotoxic to use longer-term. Newer nitroimidazoles with both aerobic and anaerobic activity, now in clinical trials, may increase the sterilizing potency of future treatment regimens.
    Antimicrobial Agents and Chemotherapy 06/2013; · 4.57 Impact Factor
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    ABSTRACT: We report a case in which F-FDG PET was able to discriminate pseudoprogression from progression observed on contrast-enhanced (CE) MRI (CE-MRI). A 56-year-old male patient with anaplastic oligodendroglioma demonstrated markedly increased tumor enhancement on CE-MRI 1 month after completing radiation therapy (RT), suggesting radiological progression. However, the patient was clinically improved and therefore received an early-therapy response assessment PET to assess for pseudoprogression. PET showed low tumor uptake indicating stable disease. Follow-up CE-MRI at 3 and 4 months post-RT confirmed stable disease. This case emphasizes the value of F-FDG PET when pseudoprogression is clinically suspected.
    Clinical nuclear medicine 03/2013; · 3.92 Impact Factor
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    ABSTRACT: The most challenging technical problem in ictal brain SPECT for localization of an epileptogenic focus is obtaining a timely injection of a radiopharmaceutical. In our institution, the first dedicated commercially available, remotely controlled automatic injector has been used in the pediatric epilepsy unit in conjunction with 24-h video and electroencephalogram monitoring. The goal of this study was to demonstrate the improved success rate of ictal injection by use of the automatic injector in the pediatric population. METHODS: Eighty-four pediatric patients and eighty-four (99m)Tc-ethylcysteinate dimer ((99m)Tc-ECD) ictal brain SPECT studies were retrospectively analyzed in a masked manner. The group with manual injection consisted of 45 studies performed from 2004 to 2010 before the introduction of the automatic injector. The group with automatic injection consisted of 39 studies performed from 2010 to 2011 after the introduction of the automatic injector. The 2 groups were comparable in the total duration of seizure, injected dose, and time from the injection to the image acquisition. The latency time from the seizure onset to the initiation time of injection, the ratio of latency time to total duration of seizure (L/T), the number of patients with repeated studies, the number of days of additional hospitalization for each study, and the localization rate for identifying a single focus in each study were compared between the groups. RESULTS: The median latency time in the group with automatic injection (8 s) was significantly lower than that of the group with manual injection (18 s) (P < 0.05). Also there was a statistically significant decrease in the number of patients with repeated studies in the group with automatic injection (2/39 [5%]), compared with the group with manual injection (14/45 [31%]) (P < 0.05). The median number of days of additional hospitalization in the group with manual injection (range, 0-7) was statistically significantly different, compared with the group with automatic injection (range, 0-1) (P < 0.05). In the group with automatic injection, 31 of 39 scans demonstrated a single localizing focus, compared to 22 of 45 scans from the manual-injection group, a significant difference (P < 0.05). The radiation exposure rate to nursing staff during the periods with automatic injection was lower than during the periods with manual injection. CONCLUSION: The automatic injector combined with 24-h video and electroencephalogram monitoring demonstrated significant clinical value by decreasing latency time, the number of patients with repeated studies, and the number of days of additional hospitalization while increasing the number of studies with a single localizing focus.
    Journal of Nuclear Medicine 03/2013; · 5.77 Impact Factor
  • Journal of Nuclear Medicine 03/2013; · 5.77 Impact Factor
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    ABSTRACT: An important research application of amyloid imaging with positron emission tomography (PET) is detection of the earliest evidence of fibrillar amyloid-beta (Aβ) deposition. Use of amyloid PET for this purpose, requires a reproducible method for defining a cutoff that separates individuals with no significant Aβ deposition from those in which Aβ deposition has begun. We previously reported the iterative outlier approach (IO) for the analysis of Pittsburgh Compound-B (PiB) PET data. Developments in amyloid imaging since the initial report of IO have led us to re-examine the generalizability of this method. IO was developed using full-dynamic atrophy-corrected PiB PET data obtained from a group of control subjects with a fairly distinct separation between PiB-positive [PiB(+)] and PiB-negative [PiB(-)] subjects. METHODS: We tested the performance of IO using late-summed tissue ratio data with atrophy correction or with an automated template method without atrophy correction and tested the robustness of the method when applied to a cohort of older subjects in which separation between PiB(+) and PiB(-) subjects was not so distinct. RESULTS: The IO method did not perform consistently across analyses and performed particularly poorly when separation was less clear. We found that a sparse k-means (SKM) cluster analysis approach performed significantly better; performing more consistently across methods and subject cohorts. We also compared SKM to a consensus visual read approach and found very good correspondence. Conclusion The visual read and SKM methods, applied together, may optimize the identification of early Aβ deposition. These methods have the potential to provide a standard approach to the detection of PiB-positivity that is generalizable across centers.
    NeuroImage 01/2013; · 6.25 Impact Factor
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    ABSTRACT: PURPOSE: To demonstrate the utility of semi-quantitative circumferential-profile analysis of regional cerebral blood flow (rCBF) SPECT in Alzheimer's disease (AD) versus white matter vascular dementia (WM-VaD). METHODS: Subjects underwent dementia evaluation, MRI and Tc-99m HMPAO SPECT. rCBF patterns from 11 AD and 20 WM-VaD patients were compared to 17 controls using semi-quantitative circumferential-profile analysis. RESULTS: AD patients showed more significant semi-quantitative circumferential-profile reductions in the posterior temporo-parietal regions, whereas WM-VaD patients demonstrated greater reductions involving the frontal regions of the brain. CONCLUSION: Semi-quantitative circumferential-profile analysis provides a practical semi-quantitative method to evaluate brain SPECT scans in AD versus WM-VaD patients.
    Computerized medical imaging and graphics: the official journal of the Computerized Medical Imaging Society 12/2012; · 1.04 Impact Factor
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    ABSTRACT: Objective: To assess the clinical utility of SPECT/ CT in subjects with endocrine and neuroendocrine tumors compared to SPECT alone. Material and Methods: 48 subjects (31 women;17 men; mean age 54±11) with clinical suspicion or diagnosis of endocrine and neuroendocrine tumor had 50 SPECT/CT scans (32 Tc-99m MIBI, 5 post treatment I-131, 8 In-111 Pentetreotide, and 5 I-123 MIBG). SPECT alone findings were compared to SPECT/CT and to pathology or radiological follow up. Results: From the 32 Tc-99m MIBI scans, SPECT accurately localized the lesion in 22 positive subjects while SPECT/CT did in 31 subjects. Parathyroid lesions not seen on SPECT alone were smaller than 10 mm. In five post treatment I-131 scans, SPECT alone neither characterized, nor localized any lesions accurately. SPECT/CT revealed 3 benign etiologies, a metastatic lymph node, and one equivocal lesion. In 8 In-111 Pentetreotide scans, SPECT alone could not localize primary or metastatic lesions in 6 subjects all of which were localized with SPECT/CT. In five I-123 MIBG scans, SPECT alone could not detect a 1.1 cm adrenal lesion or correctly characterize normal physiologic adrenal uptake in consecutive scans of the same patient with prior history of adrenelectomy, all of which were correctly localized and characterized with SPECT/CT. Conclusion: SPECT/CT is superior to SPECT alone in the assessment of endocrine and neuroendocrine tumors. It is better in lesion localization and lesion characterization leading to a decrease in the number of equivocal findings. SPECT/CT should be included in the clinical work up of all patients with diagnosis or suspicion of endocrine and neuroendocrine tumors. Conflict of interest:None declared.
    Molecular imaging and radionuclide therapy. 12/2012; 21(3):91-6.
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    ABSTRACT: This review addresses the specific contributions of nuclear medicine techniques, and especially positron emission tomography (PET), for diagnosis and management of brain tumors. (18)F-Fluorodeoxyglucose PET has particular strengths in predicting prognosis and differentiating cerebral lymphoma from nonmalignant lesions. Amino acid tracers including (11)C-methionine, (18)F-fluoroethyltyrosine, and (18)F-l-3,4-dihydroxyphenylalanine provide high sensitivity, which is most useful for detecting recurrent or residual gliomas, including most low-grade gliomas. They also play an increasing role for planning and monitoring of therapy. (18)F-fluorothymidine can only be used in tumors with absent or broken blood-brain barrier and has potential for tumor grading and monitoring of therapy. Ligands for somatostatin receptors are of particular interest in pituitary adenomas and meningiomas. Tracers to image neovascularization, hypoxia, and phospholipid synthesis are under investigation for potential clinical use. All methods provide the maximum of information when used with image registration and fusion display with contrast-enhanced magnetic resonance imaging scans. Integration of PET and magnetic resonance imaging with stereotactic neuronavigation systems allows the targeting of stereotactic biopsies to obtain a more accurate histologic diagnosis and better planning of conformal and stereotactic radiotherapy.
    Seminars in nuclear medicine 11/2012; 42(6):356-70. · 3.96 Impact Factor
  • Mandeep S Tamber, James M Mountz
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    ABSTRACT: Epilepsy is the most common serious brain disorder in children, occurring in all parts of the world and within every stratum of the population. Through its effects, it exerts a significant physical, psychological, economic, and social toll on children and their caregivers. Historically, the surgical treatment of epilepsy has been viewed with skepticism with regard to its indications, safety, and therapeutic benefit. However, continued refinements in diagnostic and operative techniques are helping to put to rest the antiquated notion that surgery is a last-resort procedure in the management of pediatric epilepsy. Surgery can be performed safely, even in infants and young children, with excellent patient outcomes in properly selected patients. This review focuses on the surgical treatment of pediatric epilepsy. A brief background discussion of seizures and epilepsy is followed by a substantive discussion regarding the intricacies of selecting patients for epilepsy surgery, emphasizing the important role of advanced imaging techniques in the decision-making process. The indications and outcomes of the most common epilepsy surgical procedures are then reviewed. The article ends with a discussion of the future of epilepsy surgery.
    Seminars in nuclear medicine 11/2012; 42(6):371-86. · 3.96 Impact Factor

Publication Stats

2k Citations
577.73 Total Impact Points

Institutions

  • 2004–2014
    • University of Pittsburgh
      • Department of Radiology
      Pittsburgh, Pennsylvania, United States
  • 2013
    • University of Virginia
      Charlottesville, Virginia, United States
    • Childrens Hospital of Pittsburgh
      Pittsburgh, Pennsylvania, United States
  • 2012
    • The University of Manchester
      Manchester, England, United Kingdom
  • 1992–2010
    • University of Alabama at Birmingham
      • • Department of Radiology
      • • Division of Clinical Immunology and Rheumatology
      • • Department of Anesthesiology
      • • Division of Nuclear Medicine
      Birmingham, AL, United States
  • 1997–1998
    • University of Alabama
      Tuscaloosa, Alabama, United States
  • 1988–1992
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
  • 1990–1991
    • University of Michigan
      • • Department of Internal Medicine
      • • Department of Psychiatry
      Ann Arbor, MI, United States