Andrei I Holodny

Weill Cornell Medical College, New York City, New York, United States

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Publications (120)251.03 Total impact

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    ABSTRACT: Functional magnetic resonance imaging (fMRI) has become a common tool for presurgical sensorimotor mapping, and is a significant preoperative asset for tumors located adjacent to the central sulcus. fMRI has changed surgical options for many patients. This noninvasive tool allows for easy display and integration with other neuroimaging techniques. Although fMRI is a useful preoperative tool, it is not perfect. Tumors that affect the normal vascular coupling of neuronal activity will affect fMRI measurements. This article discusses the usefulness of blood oxygen level dependent (BOLD) fMRI with regard to preoperative motor mapping. Copyright © 2014 Elsevier Inc. All rights reserved.
    Neuroimaging Clinics of North America 11/2014; · 1.29 Impact Factor
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    ABSTRACT: Objectives Small cell lung cancers (SCLCs) are characterized by aberrantly-methylated O6-methyl-guanine-DNA methyltransferase (MGMT). Epigenetic silencing of MGMT is associated with loss of MGMT activity and improved sensitivity to alkylating agents in glioblastomas. We have reported the activity of temozolomide, a non-classical alkylating agent, in patients with relapsed sensitive or refractory SCLCs, given at 75 mg/m2/day for 21 of 28 days. However, prolonged myelosuppression was noted. We therefore evaluated a 5-day dosing schedule of temozolomide and examined MGMT as a predictive biomarker for temozolomide treatment in SCLC. Materials and Methods Patients with sensitive or refractory SCLCs and progression after one or two prior chemotherapy regimens received temozolomide 200 mg/m2/day for 5 consecutive days in 28-day cycles. The primary endpoint was tolerability. We also assessed MGMT promoter methylation status by PCR and MGMT expression by immunohistochemistry in tumor specimens. Results Of 25 patients enrolled, 5 experienced grade 3 or 4 toxicity (anemia, thrombocytopenia, neutropenia, and constipation). The partial response rate was 12% [95% CI: 3-31%], with partial responses in 2 refractory patients. We were able to obtain tumor samples for more than half of patients for MGMT testing. Conclusion Temozolomide 200 mg/m2/day for 5 days in 28-day cycles is tolerable and active in patients with relapsed SCLCs. No treatment-limiting prolonged cytopenias were observed, making this our preferred schedule for further studies. Acquisition of archived biospecimens is feasible and necessary in order to continue evaluating the role of MGMT as a predictive biomarker in SCLCs.
    Lung Cancer 11/2014; · 3.74 Impact Factor
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    ABSTRACT: Thirty-six metastases in 22 patients were studied prospectively using computed tomography perfusion. Regions of interests were drawn around: the enhancing part of the tumor, necrotic central part, periphery, peritumoral edema, and normal white matter. Cerebral blood volume, cerebral blood flow, and mean transit time were calculated for each zone. The enhancing part of the tumor significantly differed from the other zones in 11 of 12. Metastases of different primaries can be differentiated from one another with statistically significance (P<.05) by at least one perfusion parameter in 57% of cases. Copyright © 2014 Elsevier Inc. All rights reserved.
    Clinical Imaging 10/2014; · 0.60 Impact Factor
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    ABSTRACT: Intra-axial brain schwannomas are very rare. Several case reports have described the difficulty in differentiating these lesions from more common brain tumors using conventional imaging. We present the first report documenting the MR perfusion, MR spectroscopy, and FDG-PET/CT characteristics of an intra-axial schwannoma. Although our conclusions are limited to a single case, it appears that advanced imaging may potentially be helpful in differentiating intra-axial schwannomas from other tumors that look similar on routine imaging.
    Neurographics. 09/2014; 4(3).
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    ABSTRACT: Study Design. Total of 40 patients with spinal metastases from renal cell carcinomas (RCC) or prostate carcinomas (PC) were studied using DCE (Dynamic contrast-enhanced) MRI.Objective. Our aim was to evaluate spinal metastases from RCC and PC to assess the sensitivity and specificity of perfusion parameters obtained by quantitative and semi-quantitative methods, which would allow for noninvasive discrimination between hypovascular and hypervascular lesions.Summary of Background Data. Conventional MRI can be inconclusive in assessing diagnostically complex spinal lesions in cancer patients in whom fibrosis, infarction, edema related to compression fractures, and infection may simulate malignant neoplasm. Conventional MRI is also of limited value in assessing tumor vascularity and identifying hypervascular tumors. DCE MRI offers an advantage over conventional MRI in that it provides anatomical, physiological, and hemodynamic information about neoplastic lesions.Methods. DCE perfusion parameters: vascular permeability (Ktrans), plasma volume (Vp), wash-in slope, and peak-enhancement were measured to assess their potential as discriminators of tumor vascularity. A Mann-Whitney test (at p≤0.01), was performed to quantify and compare significance of perfusion parameters between the two groups.Results. Of the four perfusion parameters studied, Vp was observed to have the largest difference in mean (μ) between PC (μ = 3.29/sec) and RCC metastases (μ = 5.92/sec). This was followed by the peak-enhancement, Ktrans, and wash-in parameters. A Mann-Whitney test showed a significant difference between Vp values for PC and RCC lesions (p≤0.001). Similarly, peak-enhancement showed a significant difference between the two histologies (p≤0.001), as did Ktrans (p≤0.01). The receiver operating characteristic curve showed that Vp recorded the highest area under the curve (0.867).Conclusion. Vp was shown to be the best discriminator between spinal metastases from PC and RCC with the mean Vp of RCC metastasis being 1.8 times that of the PC lesions, thus discriminating between hyper- and hypovascular metastases, which has important clinical implications.
    Spine 08/2014; · 2.45 Impact Factor
  • Conference Paper: Neuroradiology
    Andrei I. Holodny
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    ABSTRACT: LEARNING OBJECTIVES View learning objectives under main course title.
    Radiological Society of North America 2013 Scientific Assembly and Annual Meeting; 12/2013
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    ABSTRACT: PURPOSE Dynamic contrast enhancement MR imaging (DCE-MRI) offers noninvasive characterization of the vascular microenvironment and hemodynamics. In this study, we hypothesize that DCE-MRI can be used to evaluate treatment response and predict tumor recurrence in patients with spinal metastases undergoing high dose radiotherapy (RT). METHOD AND MATERIALS We conducted a retrospective study of 30 patients with spinal metastases who underwent DCE-MRI before and after RT. 20 patients received single-fraction SRS (24 Gy), while 10 received hypofractionated SRS (27-30 Gy total). Kaplan-Meier analysis was used to estimate the actuarial local recurrence rates, which were compared using a log-rank test. Two compartment model-based perfusion parameters (Ktrans: vascular permeability and Vp: plasma volume) were measured for each metastasis, relative to normal-appearing bone marrow. Percent change in parameter values from pre- to post-treatment were calculated and statistically compared. RESULTS At 20-month median follow-up, 5/30 (17%) patients had pathological evidence of local recurrence (LR). 3/10 (30%) patients treated with hypofractionated SRS had LR, while 2/20 (10%) patients with single-fraction SRS had LR. 1- and 3-year actuarial local recurrence rates were 24% and 44% for the hypofractionated SRS group vs. 5% and 16% for the single-fraction SRS group (p=0.20). The average change in Vp and Ktrans for patients without LR vs. those with LR was -76% (range, -99% to -12%) and -66% (range, -99% to -9%) vs. +28% (range, -19% to +102%) and -14% (range, -50% to +84%) (p<0.01 for both). For patients with LR, positive changes in perfusion parameters were observed on average 6.6 months earlier than the LR was detected on standard imaging. CONCLUSION We demonstrated that changes in perfusion, particularly Vp, reflect tumor responses to high dose RT in spinal bone metastases. Additionally, these changes predicted local tumor recurrence on average >6 months earlier than standard imaging did. CLINICAL RELEVANCE/APPLICATION The ability of DCE-MRI to detect early treatment response and predict local recurrence has the potential to improve patient care and outcome.
    Radiological Society of North America 2013 Scientific Assembly and Annual Meeting; 12/2013
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    ABSTRACT: Gross total resection of gliomas can be limited by the involvement of tumor in eloquent areas. Moreover, lesions can impart cortical reorganization and make the precise determination of hemispheric dominance and localization of language function even more difficult. Preoperative mapping with functional magnetic resonance imaging (fMRI), intraoperative imaging modalities, and intraoperative direct cortical stimulation enable surgeons to map the functional topography of the brain in relation to the tumor and perform a safe maximal resection. In this report, we present a patient with left frontal glioma of complex morphology, wherein the tumor was enveloped by Broca's area on fMRI. Intraoperative mapping and intraoperative magnetic resonance imaging (iMRI) allowed gross total resection of the tumor with preservation of language function and illustrate the utility of multiple contemporary modalities in the surgical management of low-grade gliomas located in eloquent cortices.
    Neurocase 08/2013; · 1.38 Impact Factor
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    ABSTRACT: Study Design: This was a retrospective study focusing on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to assess treatment response in patients with spinal metastases.Objective: To demonstrate DCE-MRI changes before and after radiation treatment and correlating with other imaging and clinical findings.Summary of Background Data: Currently, conventional imaging is limited in evaluating early treatment success or failure which impacts patient care.Methods: Consecutive patients with known spinal metastases underwent DCE-MRI before and after radiotherapy. Perfusion data on 19 lesions were analyzed. Radiotherapy was classified as success (n = 17) or failure (n = 2) based on evidence of tumor contraction (n = 4), negative positron emission tomography (PET) (n = 2), or stability for more than 11 months (n = 11). Perfusion parameters blood plasma volume (Vp), time-dependent leakage (Ktrans), area under the curve (AUC), and peak enhancement (PE) were derived from the signal intensity-time curves and changes in parameter values from pre- to post-treatment were calculated. Curve morphologies were also qualitatively assessed in 13 pre- and 13 post-treatment scans.Results: Vp was the strongest predictor of treatment response (false-positive rate = 9.38 × 10 and false-negative rate = 0.055). All successfully treated lesions showed decreases in Vp, and the two treatment failures showed drastic increases in Vp. Changes in AUC and PE demonstrated similar relationships to the observed treatment response, while changes in Ktrans showed no significant relationship. Signal intensity curve morphologies also demonstrated specificity for active disease (11 of 13) and treated disease (8 of 13).Conclusion: Changes in perfusion, particularly Vp, reflect tumor responses to radiotherapy in spinal bone metastases. These changes were able to predict positive outcomes earlier than 6 months after treatment in 16 of 17 tumors. The ability of DCE-MRI to detect early treatment response has the potential to improve patient care and outcome.
    Spine 07/2013; · 2.45 Impact Factor
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    ABSTRACT: Functional magnetic resonance (fMR) imaging for neurosurgical planning has become the standard of care in centers where it is available. Although paradigms to measure eloquent cortices are not yet standardized, simple tasks elicit reliable maps for planning neurosurgical procedures. A patient-specific paradigm design will refine the usability of fMR imaging for prognostication and recovery of function. Certain pathologic conditions and technical issues limit the interpretation of fMR imaging maps in clinical use and should be considered carefully. However, fMR imaging for neurosurgical planning continues to provide insights into how the brain works and how it responds to pathologic insults.
    Magnetic resonance imaging clinics of North America 05/2013; 21(2):269-78.
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    ABSTRACT: Trilateral retinoblastoma (TRb) is a rare condition in which children with bilateral retinoblastoma develop primary midline intracranial neuroblastic tumors. The intracranial lesions are difficult to follow after treatment due to residual mass-like enhancement that may represent persistent tumor or treated disease. We highlight a case where close evaluation of diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) characteristics accurately depicted the extent of treated disease versus residual tumor after chemotherapy.
    Pediatric Radiology 03/2013; · 1.65 Impact Factor
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    ABSTRACT: OBJECTIVE: Post-operative delirium is associated with pre-operative cognitive difficulties and diminished functional independence, both of which suggest that brain pathology may be present in affected individuals prior to surgery. Currently, there are few studies that have examined imaging correlates of post-operative delirium. To our knowledge, none have examined the association of delirium with existing structural pathology in pre-operative cancer patients. Here, we present a novel, retrospective strategy to assess pre-operative structural brain pathology and its association with post-operative delirium. Standard of care structural magnetic resonance imaging (MRIs) from a cohort of surgical candidates prior to surgery were analyzed for white matter hyperintensities and cerebral atrophy. METHODS: We identified 23 non-small cell lung cancer patients with no evidence of metastases in the brain pre-operatively, through retrospective chart review, who met criteria for post-operative delirium within 4 days of surgery. 24 age- and gender-matched control subjects were identified for comparison to the delirium sample. T1 and fluid-attenuated inversion recovery sequences were collected from standard of care pre-operative MRI screening and assessed for white matter pathology and atrophy. RESULTS: We found significant differences in white matter pathology between groups with the delirium group exhibiting significantly greater white matter pathology than the non-delirium group. Measure of cerebral atrophy demonstrated no significant difference between the delirium and non-delirium group. CONCLUSIONS: In this preliminary study utilizing standard of care pre-operative brain MRIs for assessment of structural risk factors to delirium, we found white matter pathology to be a significant risk factor in post-operative delirium. Limitations and implications for further investigation are discussed. Copyright © 2013 John Wiley & Sons, Ltd.
    Psycho-Oncology 03/2013; · 4.04 Impact Factor
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    ABSTRACT: The purpose of this study was to compare the deterministic and probabilistic tracking methods of diffusion tensor white matter fiber tractography in patients with brain tumors.
    Journal of Biomedical Science and Engineering 02/2013; 6(2):192-200.
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    ABSTRACT: Background and purpose Accurate localization of anatomically and functionally separate SMA tracts is important to improve planning prior to neurosurgery. Using fMRI and probabilistic DTI techniques, we assessed the connectivity between the frontal language area (Broca's area) and the rostral pre-SMA (language SMA) and caudal SMA proper (motor SMA). Materials and methods Twenty brain tumor patients completed motor and language fMRI paradigms and DTI. Peaks of functional activity in the language SMA, motor SMA and Broca's area were used to define seed regions for probabilistic tractography. Results fMRI and probabilistic tractography identified separate and unique pathways connecting the SMA to Broca's area – the language SMA pathway and the motor SMA pathway. For all subjects, the language SMA pathway had a larger number of voxels (P < 0.0001) and higher connectivity (P < 0.0001) to Broca's area than did the motor SMA pathway. In each patient, the number of voxels was greater in the language and motor SMA pathways than in background pathways (P < 0.0001). No differences were found between patients with ipsilateral and those with contralateral tumors for either the language SMA pathway (degree of connectivity: P < 0.36; number of voxels: 0.35) or the motor SMA pathway (degree of connectivity, P < 0.28; number of voxels, P < 0.74). Conclusion Probabilistic tractography can identify unique white matter tracts that connect language SMA and motor SMA to Broca's area. The language SMA is more significantly connected to Broca's area than is the motor subdivision of the SMA proper.
    Journal of Neuroradiology 01/2013; · 1.13 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE: Brain metastases from prostate cancer are uncommon and their imaging appearance has not been well defined. The main objectives of this study were to evaluate the incidence, MRI characteristics, and prognosis of parenchymal brain metastases originating in prostate cancer. METHODS: We retrospectively identified 21 patients with prostate cancer and evidence of brain metastases from 2000 to 2010. We reviewed the initial brain MRI scans and characterized the lesions according to location and appearance on MRI, while also determining patient demography, staging, and survival. RESULTS: The incidence of brain metastasis from prostate cancer was .16%. At the time of brain metastasis detection, 95% of the patients had concurrent osseous metastases, 86% lymph node metastases, and 76% liver and/or lung metastases. Brain metastases were multifocal in 71% of patients, hemorrhagic in 33%, diffusion restricted in 19%, and partially cystic/necrotic in 19%. The median overall survival after brain metastasis detection was 2.8 months. CONCLUSIONS: Brain metastasis from prostate cancer remains a rare phenomenon that most frequently occurs in the setting of widely disseminated bone and soft tissue disease. Patients with nonadenocarcinoma pathology are more likely to develop brain metastases. The MRI appearance is highly variable and prognosis is poor.
    Journal of neuroimaging: official journal of the American Society of Neuroimaging 12/2012; · 1.82 Impact Factor
  • Andrei I. Holodny
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    ABSTRACT: LEARNING OBJECTIVES 1) An overview of current medical therapies for gliomas. 2) Explain how these medical therapies affect MR Imaging characteristics. 3) How to use perfusion, diffusion, MRS to separate the effect of therapies (including pseudo-progression and pseudo-response) from true tumor biology.
    Radiological Society of North America 2012 Scientific Assembly and Annual Meeting; 11/2012
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    ABSTRACT: PURPOSE The purpose of this study is to explore the potential correlation with weakness of probabilistic tractography of the corticospinal tract (CST) in brain tumor patients. We hypothesize that differences in tractography of the CST on the tumor vs. non-tumor sides can be used to predict patient weakness. METHOD AND MATERIALS We retrospectively queried an institutional database for DTI studies in patients with unilateral enhancing brain tumors near (<2 cm from) the corticospinal tract (CST). We identified 79 patients with brain tumors (59 primary and 20 secondary tumors) and hand (n=39) and/or foot (n=29) weakness. Probabilistic tractography of the CST was implemented using DTI & FiberTools (Freiburg, Germany) using seeds placed in the motor cortex and mid pons. Quantitative measurements consisted of tumor side / non-tumor side ratios for CST volume, fractional anisotropy (FA) and mean diffusivity (MD). Qualitative grading of tumor CST morphology was performed using intact, displaced, deformed, or interrupted categories. Statistical analysis was conducted with Wilcoxon rank-sum and Fisher exact tests with p=.05. RESULTS When comparing CST ratios in patients with (n=39) and without (n=40) hand weakness, the mean volume was 0.757 vs. 1.052 (p=.015), mean FA was 0.907 vs. 0.955 (p=.009), and mean MD was 1.112 vs. 1.071 (p=.091). Morphology distribution was different between weak and non-weak patients (p=.0005), with interrupted tracts found in 8/40 (20%) weak and 0/39 non-weak. When comparing CST ratios in patients with (n=29) and without (n=50) foot weakness, the mean volume was 0.591 vs. 0.934 (p=.002), mean FA 0.920 vs. 0.951 (p=.096), and mean MD was 1.093 vs. 1.085 (p=.83). Morphology distribution was different between weak and non-weak patients (p<.0001), with interrupted tracts found in 11/29 (38%) weak and 1/50 (2%) non-weak. CONCLUSION Probabilistic tractography of the CST correlates with hand and foot weakness in patients with brain tumors, with tumor/nontumor volume ratios outperforming other measures. More work is necessary to investigate the evolution of these indicators and to evaluate potential roles in treatment decisions and monitoring. CLINICAL RELEVANCE/APPLICATION DTI tract associated metrics in brain tumor patients might serve as indicators for functional prognosis and aid in decision making in the postoperative rehabilitation and clinical management process.
    Radiological Society of North America 2012 Scientific Assembly and Annual Meeting; 11/2012
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    ABSTRACT: Patients with cancer are at high risk of developing venous thromboembolism (VTE). The purpose of this study was to review VTE development in patients undergoing craniotomy for a neoplasm, and to further analyze risk based on multiple pre-, intra-, and post-operative variables. We analyzed all consecutive patients at our institution during the years 1999-2010 who were admitted for craniotomy and had a histological diagnosis of intra-cranial neoplasm. Data points including patient demographics, length of stay, surgical time, surgical position, pre-existing comorbidities, results of extremity ultrasounds for deep venous thrombosis (DVT), and results of diagnostic pulmonary embolus (PE) studies were collected. This study was reviewed and approved by our institutional review board. A total of 1147 patients met the inclusion criteria. Nineteen percent of our patients were diagnosed with a DVT and 4.2% were diagnosed with a PE during their hospitalization. According to logistic multivariate regression analysis,
    Neuro-Oncology 11/2012; 14(suppl 6):vi86-vi90. · 5.29 Impact Factor
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    ABSTRACT: OBJECTIVES: Differentiating radiation injury from viable tumor is important for optimizing patient care. Our aim was to directly compare the effectiveness of fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) and dynamic susceptibility-weighted contrast-enhanced (DSC) magnetic resonance (MR) perfusion in differentiating radiation effects from tumor growth in patients with increased enhancement following radiotherapy for primary or secondary brain tumors. MATERIALS AND METHODS: We retrospectively identified 12 consecutive patients with primary and secondary brain tumors over a 1-year period that demonstrated indeterminate enhancing lesions after radiotherapy and that had undergone DSC MR perfusion, FDG PET-CT, and subsequent histopathologic diagnosis. The maximum standardized uptake value (SUV) of the lesion (SUV(lesion max)), SUV(ratio) (SUV(lesion max)/SUV(normal brain)), maximum relative cerebral blood volume, percentage of signal intensity recovery, and relative peak height were calculated from the positron emission tomography and MR perfusion studies. A prediction of tumor or radiation injury was made based on these variables while being blinded to the results of the surgical pathology. RESULTS: SUV(ratio) had the highest predictive value (area under the curve=0.943) for tumor progression, although this was not statistically better than any MR perfusion metric (area under the curve=0.757-0.829). CONCLUSIONS: This preliminary study suggests that FDG PET-CT and DSC MR perfusion may demonstrate similar effectiveness for distinguishing tumor growth from radiation injury. Assessment of the SUV(ratio) may increase the sensitivity and specificity of FDG PET-CT for differentiating tumor and radiation injury. Further analysis is needed to help define which modality has greater predictive capabilities.
    Clinical imaging 10/2012; · 0.73 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE:The role of DCE-MR imaging in the study of bone marrow perfusion is only partially developed, though potential applications for routine use in the clinical setting are beginning to be described. We hypothesize that DCE-MR imaging can be used to discriminate between hypervascular and hypovascular metastases based on measured perfusion variables.MATERIALS AND METHODS:We conducted a retrospective study of 26 patients using conventional MR imaging and DCE-MR imaging. Patients were assigned to a hypervascular or hypovascular group based on tumor pathology. ROIs were drawn around normal-appearing bone marrow (internal controls) and enhancing tumor areas. Average wash-in enhancement slope, average peak enhancement signal percentage change, and average peak enhancement signal percentage change in areas of highest wash-in enhancement slope were calculated. Indices were compared among control, hypervascular, and hypovascular groups. Conventional imaging was assessed by calculating pre- to postgadolinium signal percentage changes in hypervascular and hypovascular lesions.RESULTS:Hypervascular and hypovascular tumors differed significantly with regard to wash-in enhancement slope (P < .01; hypervascular 95% CI, 22.5-26.5 AU/s; hypovascular 95% CI, 14.1-20.9 AU/s) and peak enhancement signal percentage change in areas of highest wash-in enhancement slope (P < .01; hypervascular 95% CI, 174.1-323.3%; hypovascular 95% CI, 39.5-150.5%). Peak enhancement signal percentage change over all voxels was not significant (P = .62). Areas of normal-appearing marrow showed no appreciable contrast enhancement. Conventional contrast-enhanced MR imaging was unable to differentiate between hypervascular and hypovascular tumors (P = .58).CONCLUSIONS:Our data demonstrate that, unlike conventional MR imaging sequences, DCE-MR imaging may be a more accurate technique in discriminating hypervascular from hypovascular spinal metastases.
    American Journal of Neuroradiology 05/2012; · 3.17 Impact Factor

Publication Stats

1k Citations
251.03 Total Impact Points

Institutions

  • 2014
    • Weill Cornell Medical College
      New York City, New York, United States
  • 2002–2013
    • Memorial Sloan-Kettering Cancer Center
      • Department of Radiology
      New York City, New York, United States
  • 1997–2004
    • Rutgers New Jersey Medical School
      • • Department of Radiology
      • • Department of Radiology (RWJ Medical School)
      Newark, New Jersey, United States
  • 2000
    • New Jersey Institute of Technology
      Newark, New Jersey, United States
  • 1998
    • State University of New York Downstate Medical Center
      • Department of Radiology
      Brooklyn, NY, United States