Faculty Bibliography
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Idiopathic spinal cord herniation: an imaging diagnosis with a significant delay
BACKGROUND CONTEXT: Idiopathic spinal cord herniation (ISCH) is an underrecognized entity that is often underappreciated by the neurosurgery and neuroradiologic communities. This leads to delayed diagnosis, multiple imaging studies, other diagnostic tests, inappropriate surgeries, and repeat office visits. PURPOSE: To evaluate common associations between ISCH and patient demographics/clinical presentation and to analyze the potential for delayed diagnosis. PATIENT SAMPLE: Patient sample included those diagnosed with ISCH on imaging at our institution from June 20, 2005 to December 3, 2012. OUTCOME MEASURES: These were based on the patient improvement/stability/decline based on the patients' most recent clinic/office visit when compared with initial presentation. METHODS: A retrospective search of radiology reports was performed using Illuminate software from June 20, 2005 to December 3, 2012, using the search term "idiopathic spinal cord herniation." Clinical data were reviewed including patient's age, sex, presenting clinical symptoms, number and type of imaging studies performed as part of the workup, other diagnostic tests, pain procedures, surgeries, and time between original presentation and diagnosis of ISCH on imaging. RESULTS: A total of 55 patients had the search term "idiopathic spinal cord herniation" included in their radiology report, of which 37 patients were found to meet the imaging and clinical diagnosis of ISCH. The median time from presentation to imaging diagnosis was 20 months in patients younger than 60 years and 5 months in those 60 years or older (p=.02). Of the 37 patients evaluated, 27 (73%) had no change in symptoms, 5 patients (14%) experienced worsening of symptoms, and 5 (14%) experienced symptom improvement from original presentation to most recent office visit. Among all patients evaluated, three underwent repair of the ventral dural defect in ISCH, resulting in clinical improvement. There was a median of nine outpatient office visits, three magnetic resonance images (MRIs), and one electromyography (EMG) per patient presenting with ISCH. The most frequent complaints were neck/upper back pain in 70%, upper/lower extremity numbness/paresthesias/weakness in 49%, hyperreflexia in 22%, and burning chest pain in 22%. CONCLUSIONS: Prolonged time to diagnosis and subsequent treatment of ISCH protracts patient symptoms and is associated with redundant diagnostic tests and patient visits. Earlier use of MRI in younger patients (younger than 60 years) may be warranted in those with a clinical presentation suggestive of Brown-Sequard symptomatology. Increasing recognition of ISCH in imaging and surgical communities would lead to improved patient care.
PMID: 25857588
ISSN: 1878-1632
CID: 1685662
Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas
BACKGROUND: Diffuse low-grade and intermediate-grade gliomas (which together make up the lower-grade gliomas, World Health Organization grades II and III) have highly variable clinical behavior that is not adequately predicted on the basis of histologic class. Some are indolent; others quickly progress to glioblastoma. The uncertainty is compounded by interobserver variability in histologic diagnosis. Mutations in IDH, TP53, and ATRX and codeletion of chromosome arms 1p and 19q (1p/19q codeletion) have been implicated as clinically relevant markers of lower-grade gliomas. METHODS: We performed genomewide analyses of 293 lower-grade gliomas from adults, incorporating exome sequence, DNA copy number, DNA methylation, messenger RNA expression, microRNA expression, and targeted protein expression. These data were integrated and tested for correlation with clinical outcomes. RESULTS: Unsupervised clustering of mutations and data from RNA, DNA-copy-number, and DNA-methylation platforms uncovered concordant classification of three robust, nonoverlapping, prognostically significant subtypes of lower-grade glioma that were captured more accurately by IDH, 1p/19q, and TP53 status than by histologic class. Patients who had lower-grade gliomas with an IDH mutation and 1p/19q codeletion had the most favorable clinical outcomes. Their gliomas harbored mutations in CIC, FUBP1, NOTCH1, and the TERT promoter. Nearly all lower-grade gliomas with IDH mutations and no 1p/19q codeletion had mutations in TP53 (94%) and ATRX inactivation (86%). The large majority of lower-grade gliomas without an IDH mutation had genomic aberrations and clinical behavior strikingly similar to those found in primary glioblastoma. CONCLUSIONS: The integration of genomewide data from multiple platforms delineated three molecular classes of lower-grade gliomas that were more concordant with IDH, 1p/19q, and TP53 status than with histologic class. Lower-grade gliomas with an IDH mutation either had 1p/19q codeletion or carried a TP53 mutation. Most lower-grade gliomas without an IDH mutation were molecularly and clinically similar to glioblastoma. (Funded by the National Institutes of Health.).
PMCID:4530011
PMID: 26061751
ISSN: 1533-4406
CID: 1685142
Glioma Angiogenesis and Perfusion Imaging: Understanding the Relationship between Tumor Blood Volume and Leakiness with Increasing Glioma Grade
BACKGROUND AND PURPOSE: The purpose of this study was to investigate imaging correlates to the changes occurring during angiogenesis in gliomas. This was accomplished through in vivo assessment of vascular parameters (relative CBV and permeability surface-area product) and their changing relationship with increasing glioma grade. MATERIALS AND METHODS: Seventy-six patients with gliomas underwent preoperative perfusion CT and assessment of relative CBV and permeability surface-area product. Regression analyses were performed to assess the rate of change between relative CBV and permeability surface-area product and to test whether these differed for distinct glioma grades. The ratio of relative CBV to permeability surface-area product was also computed and compared among glioma grades by using analysis of variance methods. RESULTS: The rate of change in relative CBV with respect to permeability surface-area product was highest for grade II gliomas followed by grade III and then grade IV (1.64 versus 0.91 versus 0.27, respectively). The difference in the rate of change was significant between grade III and IV (P = .003) and showed a trend for grades II and IV (P = .098). Relative CBV/permeability surface-area product ratios were the highest for grade II and lowest for grade IV. The pair-wise difference among all 3 groups was significant (P < .001). CONCLUSIONS: There is an increase in relative CBV more than permeability surface-area product in lower grade gliomas, whereas in grade III and especially grade IV gliomas, permeability surface-area product increases much more than relative CBV. The rate of change of relative CBV with respect to permeability surface-area product and relative CBV/permeability surface-area product ratio can serve as an imaging correlate to changes occurring at the tumor microvasculature level.
PMID: 26206809
ISSN: 1936-959x
CID: 1684132
Perfusion Imaging in Neuro-Oncology: Basic Techniques and Clinical Applications
Perfusion imaging is a method for assessing the flow of blood occurring at the tissue level and can be accomplished by both CT and MR perfusion techniques. The use of perfusion imaging has increased substantially in the past decade, particularly in neuro-oncologic imaging, where it is has been used for brain tumor grading and directing biopsies or targeted therapy, as well as for the evaluation of treatment response and disease progression. This article discusses the basic principles and techniques of perfusion imaging, as well as its applications in neuro-oncology.
PMID: 25953286
ISSN: 1557-8275
CID: 1639742
Clinical predictors of abnormal magnetic resonance imaging findings in patients with asymmetric sensorineural hearing loss
IMPORTANCE: Asymmetric sensorineural hearing loss (ASNHL) is commonly encountered in an otolaryngologic clinical practice. Determining what factors are associated with abnormal magnetic resonance imaging (MRI) findings will help with diagnostic workup. OBJECTIVE: To evaluate the association between clinical and audiometric factors and abnormal MRI findings in patients with ASNHL. DESIGN, SETTING, AND PARTICIPANTS: Retrospective medical record review from an urban, tertiary referral center of 451 patients with ASNHL who underwent MRI testing between January 2005 and December 2011. MAIN OUTCOMES AND MEASURES: Medical records were reviewed for audiometric parameters as well as clinical presentation and compared with MRI results, which were categorized as abnormal, normal, or incidental. Data analysis included chi2 tests, logistic regression analysis, and multivariate analysis. RESULTS: A total of 48 patients (10.6%) had abnormal MRI findings. Only 21 patients (4.7%) had a mass of the cerebellopontine angle/internal auditory canal on MRI, making up 40% of all abnormal MRI findings. The next most common MRI finding was labyrinthitis (n = 13; 25%). Vertigo/dizziness (n = 20; P = .01), tinnitus (n = 18; P = .02), sudden hearing loss (n = 15; P = .054), and 15-dB asymmetry at 3 kHz (n = 39; P = .01) were associated with abnormal MRI findings. Loud noise exposure was associated with normal MRI findings. Logistic regression analysis showed that vertigo/dizziness (odds ratio [OR], 2.14; 95% CI, 1.15-3.96; P = .02), unilateral tinnitus (OR, 2.15; 95% CI, 1.14-4.03; P = .02), and 15-dB asymmetry at 3 kHz (OR, 2.62; 95% CI, 1.24-5.57; P = .01) were significantly associated with abnormal MRI findings. Multivariate analysis showed that only 15-dB asymmetry at 3 kHz (OR, 2.42; 95% CI, 1.07-5.50; P = .03) was significantly associated with an abnormal MRI finding. CONCLUSIONS AND RELEVANCE: This study found that asymmetry of 15 dB at 3 kHz on audiometry was associated with higher positive yield on use of MRI in evaluating patients with ASNHL. We recommend that patients who present with ASNHL with this audiometric characteristic undergo MRI as part of their diagnostic workup.
PMID: 25719460
ISSN: 2168-619x
CID: 1602512
Diffusion MRI quality control and functional diffusion map results in ACRIN 6677/RTOG 0625: A multicenter, randomized, phase II trial of bevacizumab and chemotherapy in recurrent glioblastoma
Functional diffusion mapping (fDM) is a cancer imaging technique that quantifies voxelwise changes in apparent diffusion coefficient (ADC). Previous studies have shown value of fDMs in bevacizumab therapy for recurrent glioblastoma multiforme (GBM). The aim of the present study was to implement explicit criteria for diffusion MRI quality control and independently evaluate fDM performance in a multicenter clinical trial (RTOG 0625/ACRIN 6677). A total of 123 patients were enrolled in the current multicenter trial and signed institutional review board-approved informed consent at their respective institutions. MRI was acquired prior to and 8 weeks following therapy. A 5-point QC scoring system was used to evaluate DWI quality. fDM performance was evaluated according to the correlation of these metrics with PFS and OS at the first follow-up time-point. Results showed ADC variability of 7.3% in NAWM and 10.5% in CSF. A total of 68% of patients had usable DWI data and 47% of patients had high quality DWI data when also excluding patients that progressed before the first follow-up. fDM performance was improved by using only the highest quality DWI. High pre-treatment contrast enhancing tumor volume was associated with shorter PFS and OS. A high volume fraction of increasing ADC after therapy was associated with shorter PFS, while a high volume fraction of decreasing ADC was associated with shorter OS. In summary, DWI in multicenter trials are currently of limited value due to image quality. Improvements in consistency of image quality in multicenter trials are necessary for further advancement of DWI biomarkers.
PMCID:4383029
PMID: 25672376
ISSN: 1791-2423
CID: 1522932
Imaging genomic mapping of an invasive MRI phenotype predicts patient outcome and metabolic dysfunction: a TCGA glioma phenotype research group project
BACKGROUND:Invasion of tumor cells into adjacent brain parenchyma is a major cause of treatment failure in glioblastoma. Furthermore, invasive tumors are shown to have a different genomic composition and metabolic abnormalities that allow for a more aggressive GBM phenotype and resistance to therapy. We thus seek to identify those genomic abnormalities associated with a highly aggressive and invasive GBM imaging-phenotype. METHODS:We retrospectively identified 104 treatment-naïve glioblastoma patients from The Cancer Genome Atlas (TCGA) whom had gene expression profiles and corresponding MR imaging available in The Cancer Imaging Archive (TCIA). The standardized VASARI feature-set criteria were used for the qualitative visual assessments of invasion. Patients were assigned to classes based on the presence (Class A) or absence (Class B) of statistically significant invasion parameters to create an invasive imaging signature; imaging genomic analysis was subsequently performed using GenePattern Comparative Marker Selection module (Broad Institute). RESULTS:Our results show that patients with a combination of deep white matter tracts and ependymal invasion (Class A) on imaging had a significant decrease in overall survival as compared to patients with absence of such invasive imaging features (Class B) (8.7 versus 18.6 months, p < 0.001). Mitochondrial dysfunction was the top canonical pathway associated with Class A gene expression signature. The MYC oncogene was predicted to be the top activation regulator in Class A. CONCLUSION/CONCLUSIONS:We demonstrate that MRI biomarker signatures can identify distinct GBM phenotypes associated with highly significant survival differences and specific molecular pathways. This study identifies mitochondrial dysfunction as the top canonical pathway in a very aggressive GBM phenotype. Thus, imaging-genomic analyses may prove invaluable in detecting novel targetable genomic pathways.
PMCID:4057583
PMID: 24889866
ISSN: 1755-8794
CID: 2912022
NCI Workshop Report: Clinical and Computational Requirements for Correlating Imaging Phenotypes with Genomics Signatures
The National Cancer Institute (NCI) Cancer Imaging Program organized two related workshops on June 26-27, 2013, entitled "Correlating Imaging Phenotypes with Genomics Signatures Research" and "Scalable Computational Resources as Required for Imaging-Genomics Decision Support Systems." The first workshop focused on clinical and scientific requirements, exploring our knowledge of phenotypic characteristics of cancer biological properties to determine whether the field is sufficiently advanced to correlate with imaging phenotypes that underpin genomics and clinical outcomes, and exploring new scientific methods to extract phenotypic features from medical images and relate them to genomics analyses. The second workshop focused on computational methods that explore informatics and computational requirements to extract phenotypic features from medical images and relate them to genomics analyses and improve the accessibility and speed of dissemination of existing NIH resources. These workshops linked clinical and scientific requirements of currently known phenotypic and genotypic cancer biology characteristics with imaging phenotypes that underpin genomics and clinical outcomes. The group generated a set of recommendations to NCI leadership and the research community that encourage and support development of the emerging radiogenomics research field to address short-and longer-term goals in cancer research.
PMCID:4225695
PMID: 25389451
ISSN: 1936-5233
CID: 1471432
Differentiating shunt-responsive normal pressure hydrocephalus from Alzheimer disease and normal aging: pilot study using automated MRI brain tissue segmentation
Evidence suggests that normal pressure hydrocephalus (NPH) is underdiagnosed in day to day radiologic practice, and differentiating NPH from cerebral atrophy due to other neurodegenerative diseases and normal aging remains a challenge. To better characterize NPH, we test the hypothesis that a prediction model based on automated MRI brain tissue segmentation can help differentiate shunt-responsive NPH patients from cerebral atrophy due to Alzheimer disease (AD) and normal aging. Brain segmentation into gray and white matter (GM, WM), and intracranial cerebrospinal fluid was derived from pre-shunt T1-weighted MRI of 15 shunt-responsive NPH patients (9 men, 72.6 +/- 8.0 years-old), 17 AD patients (10 men, 72.1 +/- 11.0 years-old) chosen as a representative of cerebral atrophy in this age group; and 18 matched healthy elderly controls (HC, 7 men, 69.7 +/- 7.0 years old). A multinomial prediction model was generated based on brain tissue volume distributions. GM decrease of 33 % relative to HC characterized AD (P < 0.005). High preoperative ventricular and near normal GM volumes characterized NPH. A multinomial regression model based on gender, GM and ventricular volume had 96.3 % accuracy differentiating NPH from AD and HC. In conclusion, automated MRI brain tissue segmentation differentiates shunt-responsive NPH with high accuracy from atrophy due to AD and normal aging. This method may improve diagnosis of NPH and improve our ability to distinguish normal from pathologic aging.
PMID: 25082631
ISSN: 0340-5354
CID: 1090402
Measurement of rat brain tumor kinetics using an intravascular MR contrast agent and DCE-MRI nested model selection
PURPOSE: Using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in a rat glioma model, and nested model selection (NMS), to compare estimates of the pharmacokinetic parameters vp , Ktrans , and ve for two different contrast agents (CAs)-gadofosveset, which reversibly binds to human serum albumin, and gadopentetate dimeglumine, which does not. MATERIALS AND METHODS: DCE-MRI studies were performed on nine Fisher 344 rats inoculated intracerebrally with 9L gliosarcoma cells using both gadofosveset and gadopentetate. The parameters vp , Ktrans , and ve were estimated using NMS. RESULTS: Ktrans estimates using gadofosveset, compared to gadopentetate, differed in their means (gadofosveset 0.025 +/- 0.008 min-1 vs. gadopentetate 0.046 +/- 0.011 min-1 ; P = 0.0039). This difference notwithstanding, the intraclass correlation coefficient (ICC) for the two estimates of Ktrans showed nearly perfect linear dependence (ICC = 0.8479 by Pearson's r). Other estimates, ve (gadofosveset 22.7 +/- 4.7% vs. gadopentetate 23.6 +/- 5.6%; P = 0.4258) and vp (gadofosveset 1.5 +/- 0.5% vs. gadopentetate 1.6 +/- 0.4%; P = 0.25), were not different in their means between the two CAs, and there was almost perfect agreement for ve (ICC = 0.8798) and substantial agreement for vp (ICC = 0.7981) between the two CAs. CONCLUSION: Estimates of Ktrans were statistically different using gadofosveset and gadopentetate, whereas ve and vp were similar with two CAs. NMS produced robust estimates of pharmacokinetic parameters using DCE-MRI that show promise as important measures of tumor physiology and microenvironment. J. Magn. Reson. Imaging 2014;. (c) 2014 Wiley Periodicals, Inc.
PMCID:4686270
PMID: 24421265
ISSN: 1053-1807
CID: 950902
