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Edmond A. Knopp

Bio: Edmond A. Knopp is an academic researcher from New York University. The author has contributed to research in topics: Magnetic resonance imaging & Bevacizumab. The author has an hindex of 30, co-authored 66 publications receiving 5822 citations. Previous affiliations of Edmond A. Knopp include Maimonides Medical Center & University of California, San Francisco.


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Journal Article
TL;DR: The rCBV measurements had the most superior diagnostic performance (either with or without metabolite ratios) in predicting glioma grade and can be used in a clinical setting to evaluate tumors preoperatively for histologic grade and provide a means for guiding treatment and predicting postoperative patient outcome.
Abstract: BACKGROUND AND PURPOSE: Sensitivity, positive predictive value (PPV), and negative predictive value (NPV) of conventional MR imaging in predicting glioma grade are not high. Relative cerebral blood volume (rCBV) measurements derived from perfusion MR imaging and metabolite ratios from proton MR spectroscopy are useful in predicting glioma grade. We evaluated the sensitivity, specificity, PPV, and NPV of perfusion MR imaging and MR spectroscopy compared with conventional MR imaging in grading primary gliomas. METHODS: One hundred sixty patients with a primary cerebral glioma underwent conventional MR imaging, dynamic contrast-enhanced T2*-weighted perfusion MR imaging, and proton MR spectroscopy. Gliomas were graded as low or high based on conventional MR imaging findings. The rCBV measurements were obtained from regions of maximum perfusion. Metabolite ratios (choline [Cho]/creatine [Cr], Cho/N-acetylaspartate [NAA], and NAA/Cr) were measured at a TE of 144 ms. Tumor grade determined with the three methods was then compared with that from histopathologic grading. Logistic regression and receiver operating characteristic analyses were performed to determine optimum thresholds for tumor grading. Sensitivity, specificity, PPV, and NPV for identifying high-grade gliomas were also calculated. RESULTS: Sensitivity, specificity, PPV, and NPV for determining a high-grade glioma with conventional MR imaging were 72.5%, 65.0%, 86.1%, and 44.1%, respectively. Statistical analysis demonstrated a threshold value of 1.75 for rCBV to provide sensitivity, specificity, PPV, and NPV of 95.0%, 57.5%, 87.0%, and 79.3%, respectively. Threshold values of 1.08 and 1.56 for Cho/Cr and 0.75 and 1.60 for Cho/NAA provided the minimum C2 and C1 errors, respectively, for determining a high-grade glioma. The combination of rCBV, Cho/Cr, and Cho/NAA resulted in sensitivity, specificity, PPV, and NPV of 93.3%, 60.0%, 87.5%, and 75.0%, respectively. Significant differences were noted in the rCBV and Cho/Cr, Cho/NAA, and NAA/Cr ratios between low- and high-grade gliomas (P CONCLUSION: The rCBV measurements and metabolite ratios both individually and in combination can increase the sensitivity and PPV when compared with conventional MR imaging alone in determining glioma grade. The rCBV measurements had the most superior diagnostic performance (either with or without metabolite ratios) in predicting glioma grade. Threshold values can be used in a clinical setting to evaluate tumors preoperatively for histologic grade and provide a means for guiding treatment and predicting postoperative patient outcome.

1,014 citations

Journal ArticleDOI
TL;DR: Echo-planar perfusion imaging is useful in the preoperative assessment of tumor grade and in providing diagnostic information not available with conventional MR imaging.
Abstract: PURPOSE: To evaluate the role of T2*-weighted echo-planar perfusion imaging by using a first-pass gadopentetate dimeglumine technique to determine the association of magnetic resonance (MR) imaging–derived cerebral blood volume (CBV) maps with histopathologic grading of astrocytomas and to improve the accuracy of targeting of stereotactic biopsy. MATERIALS AND METHODS: MR imaging was performed in 29 patients by using a first-pass gadopentetate dimeglumine T2*-weighted echo-planar perfusion sequence followed by conventional imaging. The perfusion data were processed to obtain a color map of relative regional CBV. This information formed the basis for targeting the stereotactic biopsy. Relative CBV values were computed with a nondiffusible tracer model. The relative CBV of lesions was expressed as a percentage of the relative CBV of normal white matter. The maximum relative CBV of each lesion was correlated with the histopathologic grading of astrocytomas obtained from samples from stereotactic biopsy or vo...

587 citations

Journal ArticleDOI
TL;DR: Although conventional MR imaging characteristics of solitary metastases and primary high-grade gliomas may sometimes be similar, perfusion-weighted and spectroscopic MR imaging enable distinction between the two.
Abstract: PURPOSE: To determine whether perfusion-weighted and proton spectroscopic MR imaging can be used to differentiate high-grade primary gliomas and solitary metastases on the basis of differences in vascularity and metabolite levels in the peritumoral region. MATERIALS AND METHODS: Fifty-one patients with a solitary brain tumor (33 gliomas, 18 metastases) underwent conventional, contrast material–enhanced perfusion-weighted, and proton spectroscopic MR imaging before surgical resection or stereotactic biopsy. Of the 33 patients with gliomas, 22 underwent perfusion-weighted MR imaging; nine, spectroscopic MR imaging; and two underwent both. Of the 18 patients with metastases, 12 underwent perfusion-weighted MR imaging, and six, spectroscopic MR imaging. The peritumoral region was defined as the area in the white matter immediately adjacent to the enhancing (hyperintense on T2-weighted images, but not enhancing on postcontrast T1-weighted images) portion of the tumor. Relative cerebral blood volumes in these r...

527 citations

Journal ArticleDOI
TL;DR: The clinical applications of cerebral blood volume maps obtained with perfusion MR imaging in the differential diagnosis of intracranial mass lesions, as well as the pitfalls and limitations of the technique are discussed.
Abstract: Dynamic contrast agent-enhanced perfusion magnetic resonance (MR) imaging provides physiologic information that complements the anatomic information available with conventional MR imaging. Analysis of dynamic data from perfusion MR imaging, based on tracer kinetic theory, yields quantitative estimates of cerebral blood volume that reflect the underlying microvasculature and angiogenesis. Perfusion MR imaging is a fast and robust imaging technique that is increasingly used as a research tool to help evaluate and understand intracranial disease processes and as a clinical tool to help diagnose, manage, and understand intracranial mass lesions. With the increasing number of applications of perfusion MR imaging, it is important to understand the principles underlying the technique. In this review, the essential underlying physics and methods of dynamic contrast-enhanced susceptibility-weighted echo-planar perfusion MR imaging are described. The clinical applications of cerebral blood volume maps obtained with perfusion MR imaging in the differential diagnosis of intracranial mass lesions, as well as the pitfalls and limitations of the technique, are discussed. Emphasis is on the clinical role of perfusion MR imaging in providing insight into the underlying pathophysiology of cerebral microcirculation.

498 citations

Journal Article
TL;DR: In this paper, the associations between relative cerebral blood volume (rCBV) and vascular permeability (Ktrans) derived from dynamic, susceptibility-weighted, contrastenhanced (DSC) MR imaging and tumor grade and between rCBV and Ktrans were assessed.
Abstract: BACKGROUND AND PURPOSE: Relative cerebral blood volume (rCBV) and vascular permeability (Ktrans) permit in vivo assessment of glioma microvasculature. We assessed the associations between rCBV and Ktrans derived from dynamic, susceptibility-weighted, contrast-enhanced (DSC) MR imaging and tumor grade and between rCBV and Ktrans. METHODS: Seventy-three patients with primary gliomas underwent conventional and DSC MR imaging. rCBVs were obtained from regions of maximal abnormality for each lesion on rCBV color maps. Ktrans was derived from a pharmacokinetic modeling algorithm. Histopathologic grade was compared with rCBV and Ktrans (Tukey honestly significant difference). Spearman and Pearson correlation factors were determined between rCBV, Ktrans, and tumor grade. The diagnostic utility of rCBV and Ktrans in discriminating grade II or III tumors from grade I tumors was assessed by logistic regression. RESULTS: rCBV was significantly different for all three grades (P ≤ .0005). Ktrans was significantly different between grade I and grade II or III (P = .027) but not between other grades or combinations of grades. Spearman rank and Pearson correlations, respectively, were as follows: rCBV and grade, r = 0.817 and r = 0.771; Ktrans and grade, r = 0.234 and r = 0.277; and rCBV and Ktrans, r = 0.266 and r = 0.163. Only rCBV was significantly predictive of high-grade gliomas (P CONCLUSION: rCBV with strongly correlated with tumor grade; the correlation between Ktrans and tumor grade was weaker. rCBV and Ktrans were positively but weakly correlated, suggesting that these parameters demonstrate different tumor characteristics. rCBV is a more significant predictor of high-grade glioma than Ktrans.

475 citations


Cited by
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TL;DR: The authors found that approximately 5% of patients with malignant gliomas have a family history of glioma and most of these familial cases are associated with rare genetic syndromes, such as neurofibromatosis types 1 and 2, the Li−Fraumeni syndrome (germ-line p53 mutations associated with an increased risk of several cancers), and Turcot's syndrome (intestinal polyposis and brain tumors).
Abstract: Approximately 5% of patients with malignant gliomas have a family history of gliomas. Some of these familial cases are associated with rare genetic syndromes, such as neurofibromatosis types 1 and 2, the Li−Fraumeni syndrome (germ-line p53 mutations associated with an increased risk of several cancers), and Turcot’s syndrome (intestinal polyposis and brain tumors). 10 However, most familial cases have

3,823 citations

Journal ArticleDOI
TL;DR: The recognition that contrast enhancement is nonspecific and may not always be a true surrogate of tumor response and the need to account for the nonenhancing component of the tumor mandate that new criteria be developed and validated to permit accurate assessment of the efficacy of novel therapies.
Abstract: Currently, the most widely used criteria for assessing response to therapy in high-grade gliomas are based on two-dimensional tumor measurements on computed tomography (CT) or magnetic resonance imaging (MRI), in conjunction with clinical assessment and corticosteroid dose (the Macdonald Criteria). It is increasingly apparent that there are significant limitations to these criteria, which only address the contrast-enhancing component of the tumor. For example, chemoradiotherapy for newly diagnosed glioblastomas results in transient increase in tumor enhancement (pseudoprogression) in 20% to 30% of patients, which is difficult to differentiate from true tumor progression. Antiangiogenic agents produce high radiographic response rates, as defined by a rapid decrease in contrast enhancement on CT/MRI that occurs within days of initiation of treatment and that is partly a result of reduced vascular permeability to contrast agents rather than a true antitumor effect. In addition, a subset of patients treated with antiangiogenic agents develop tumor recurrence characterized by an increase in the nonenhancing component depicted on T2-weighted/fluid-attenuated inversion recovery sequences. The recognition that contrast enhancement is nonspecific and may not always be a true surrogate of tumor response and the need to account for the nonenhancing component of the tumor mandate that new criteria be developed and validated to permit accurate assessment of the efficacy of novel therapies. The Response Assessment in Neuro-Oncology Working Group is an international effort to develop new standardized response criteria for clinical trials in brain tumors. In this proposal, we present the recommendations for updated response criteria for high-grade gliomas.

3,077 citations

Journal ArticleDOI
TL;DR: It is reported that angiogenesis inhibitors targeting the VEGF pathway demonstrate antitumor effects in mouse models of pancreatic neuroendocrine carcinoma and glioblastoma but concomitantly elicit tumor adaptation and progression to stages of greater malignancy, with heightened invasiveness and in some cases increased lymphatic and distant metastasis.

2,303 citations

Journal ArticleDOI
TL;DR: This study provides insight into different mechanisms of action of this class of drugs in recurrent glioblastoma patients and suggests that the timing of combination therapy may be critical for optimizing activity against this tumor.

1,709 citations