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High cerebral blood volume in human gliomas predicts deletion of chromosome 1p: Preliminary results of molecular studies in gliomas with elevated perfusion

Law, Meng; Brodsky, Jennie E; Babb, James; Rosenblum, Marc; Miller, Douglas C; Zagzag, David; Gruber, Michael L; Johnson, Glyn
PURPOSE: To determine if increased perfusion using dynamic susceptibility contrast perfusion MRI (DSC MRI) in gliomas may be predictive of 1p19q deletions. Loss of heterozygosity of chromosomes 1p and 19q confers responsiveness to chemotherapy improving survival in gliomas. MATERIALS AND METHODS: We retrospectively reviewed 16 patients who had DSC MRI and molecular studies of their excised gliomas for 1p19q deletions. Allelic status was assessed by loss of heterozygosity using polymerase chain reaction (PCR). DNA was extracted from paraffin curls of brain tumor sections and nail clippings. Relative cerebral blood volume (rCBV) measurements were then statistically compared with the presence of 1p and 19q deletions. RESULTS: Patients with 1p19q deletions (N = 7) demonstrated rCBV values of 10.54 +/- 2.93. Patients without 1p deletions (N = 9) had rCBV values of 4.84 +/- 2.4 (P = 0.012). Logistic regression demonstrated that rCBV was able to predict the presence of a 1p deletion to significance levels of 0.038 and 0.044, adjusted and not adjusted for age and sex, respectively. The kappa coefficient for the agreement between predicted deletion status using rCBV and the truedeletion status was 0.746 (P = 0.0028). Deletions of 19q alone, or together with 1p deletions, were not associated with high rCBV. CONCLUSION: Histopathologic, molecular, and imaging evidence supports increased neovascularity in gliomas with 1p deletions in this preliminary study. We propose a diagnostic algorithm to obtain molecular studies in gliomas demonstrating high rCBV.
PMID: 17520715
ISSN: 1053-1807
CID: 73001

Dynamic sagittal half-Fourier acquired single-shot turbo spin-echo MR imaging of the temporomandibular joint: initial experience and comparison with sagittal oblique proton-attenuation images

Wang, E Y; Mulholland, T P; Pramanik, B K; Nusbaum, A O; Babb, J; Pavone, A G; Fleisher, K E
BACKGROUND AND PURPOSE: Our aim was to assess dynamic half-Fourier acquired single-shot turbo spin-echo (HASTE) MR imaging of the temporomandibular joint (TMJ) using parallel imaging, in comparison with static proton density (Pd) imaging. MATERIALS AND METHODS: Thirty-four TMJs from 17 subjects (7 volunteers, 10 patients) were imaged in a multichannel head coil on a 1.5 T magnet by using a 35-second dynamic sagittal HASTE acquisition (TR/TE, 1180/65 msec; matrix, 128 x 128; section thickness, 7 mm; 30 images) and sagittal oblique Pd in closed- and open-mouthed positions (TR/TE, 1800/12 msec; matrix, 256 x 256; section thickness, 2 mm; 15 sections). Images were reviewed by 3 readers and rated for confidence of disk position, presence of motion artifact, range of motion, and presence of disk displacement on a 5-point scale. Consensus review of cases was also performed to assess disk dislocation and limited range of motion. RESULTS: More static examinations were rated as having motion artifact (19.6% versus 6.9%, P=.016), limited range of motion (30.4% versus 17.7%, P=.016), and disk dislocations (31.4% versus 22.6%, P=.071). Confidence ratings were higher on dynamic examinations (4.11 versus 3.74, P=.018). Chi-squared tests demonstrated no significant difference in consensus reviews of the 2 examination types. CONCLUSION: Dynamic HASTE TMJ MR imaging is a time-efficient adjunct to standard MR imaging protocols, producing fewer motion artifacts, additional range of motion information, and a dynamic assessment of disk position, when compared with static imaging. Further study is needed to evaluate the role of this sequence in diagnosing disk displacement
PMID: 17569972
ISSN: 0195-6108
CID: 73383

Proton MR spectroscopy and MRI-volumetry in mild traumatic brain injury

Cohen, B A; Inglese, M; Rusinek, H; Babb, J S; Grossman, R I; Gonen, O
BACKGROUND AND PURPOSE: More than 85% of brain traumas are classified as 'mild'; MR imaging findings are minimal if any and do not correspond to clinical symptoms. Our goal, therefore, was to quantify the global decline of the neuronal marker N-acetylaspartate (NAA), as well as gray (GM) and white matter (WM) atrophy after mild traumatic brain injury (mTBI). MATERIALS AND METHODS: Twenty patients (11 male, 9 female; age range, 19-57 years; median, 35 years) with mTBI (Glasgow Coma Scale score 13-15 with loss of consciousness for at least 30 seconds) and 19 age- and sex-matched control subjects were studied. Seven patients were studied within 9 days of TBI; the other 13 ranged from 1.2 months to 31.5 years (average and median of 4.6 and 1.7 years, respectively) after injury. Whole-brain NAA (WBNAA) concentration was obtained in all subjects with nonlocalizing proton MR spectroscopy. Brain volume and GM and WM fractions were segmented from T1-weighted MR imaging and normalized to the total intracranial volume, suitable for intersubject comparisons. The data were analyzed with least squares regression. RESULTS: Patients with mTBI exhibited, on average, a 12% WBNAA deficit that increased with age, compared with the control subjects (p<.05). Adjusted for age effects, patients also suffered both global atrophy (-1.09%/year; P=.029) and GM atrophy (-0.89%/year; P=.042). Patients with and without visible MR imaging pathology, typically punctate foci of suspected shearing injury, were indistinguishable in both atrophy and WBNAA. CONCLUSION: WBNAA detected neuronal/axonal injury beyond the minimal focal MR-visible lesions in mTBI. Combined with GM atrophy, the findings may provide further, noninvasive insight into the nature and progression of mTBI
PMID: 17494667
ISSN: 0195-6108
CID: 73233

The utility of the plain radiograph "shunt series" in the evaluation of suspected ventriculoperitoneal shunt failure in pediatric patients

Desai, Kapil R; Babb, James S; Amodio, John B
BACKGROUND: To our knowledge, the sensitivity of plain radiography, known as the shunt series, in diagnosing an etiology of ventriculoperitoneal (VP) shunt malfunction in children has not been previously investigated. OBJECTIVE: To determine the accuracy of plain radiography in diagnosing VP shunt failure in children in whom shunt malfunction is clinically suspected. MATERIALS AND METHODS: We retrospectively reviewed the charts of 238 children who had undergone plain radiographic examination for evaluation of clinically suspected VP shunt failure over a 5-year period. The results were compared with those of CT, MRI, and nuclear cisternography. RESULTS: Just 6.72% of patients demonstrated plain radiographic signs of shunt failure. Of patients with normal plain radiographs, 43% demonstrated shunt abnormalities on CT, MRI or cisternography. Statistical analysis indicated that no more than 10.46% (P < 0.05) of plain radiographs showed signs of failure and that the sensitivity of plain radiography for the detection of VP shunt failure is no higher than 31%. Furthermore, there was poor agreement between the results of plain radiography and those of CT, MRI and cisternography. CONCLUSION: Children with clinically suspected VP shunt failure should proceed directly to cross-sectional or nuclear imaging, as plain radiographic examinations have low sensitivity and significant false-negative rates for detecting shunt abnormalities in all-comers. Use of the shunt series should be limited to patients who specifically have suspected mechanical causes of shunt failure
PMID: 17380325
ISSN: 0301-0449
CID: 75356

Quantitative MRI reveals aging-associated T2 changes in mouse models of Alzheimer's disease

Falangola, M F; Dyakin, V V; Lee, S P; Bogart, A; Babb, J S; Duff, K; Nixon, R; Helpern, J A
In this study, we used MRI to analyze quantitative parametric maps of transverse (T(2)) relaxation times in a longitudinal study of transgenic mice expressing mutant forms of amyloid precursor protein (APP), presenilin (PS1), or both (PS/APP), modeling aspects of Alzheimer's disease (AD). The main goal was to characterize the effects of progressive beta-amyloid accumulation and deposition on the biophysical environment of water and to investigate if these measurements would provide early indirect evidence of AD pathological changes in the brains of these mice. Our results demonstrate that at an early age before beta-amyloid deposition, only PS/APP mice show a reduced T(2) in the hippocampus and cortex compared with wild-type non-transgenic (NTg) controls, whereas a statistically significant within-group aging-associated decrease in T(2) values is seen in the cortex and hippocampus of all three transgenic genotypes (APP, PS/APP, and PS) but not in the NTg controls. In addition, for animals older than 12 months, we confirmed our previous report that only the two genotypes that form amyloid plaques (APP and PS/APP) have significantly reduced T(2) values compared with NTg controls. Thus, T(2) changes in these AD models can precede amyloid deposition or even occur in AD models that do not deposit beta-amyloid (PS mice), but are intensified in the presence of amyloid deposition
PMID: 17451178
ISSN: 0952-3480
CID: 91355

Histogram analysis versus region of interest analysis of dynamic susceptibility contrast perfusion MR imaging data in the grading of cerebral gliomas

Law, M; Young, R; Babb, J; Pollack, E; Johnson, G
BACKGROUND AND PURPOSE: Histogram analysis can be applied to dynamic susceptibility contrast (DSC) perfusion MR imaging datasets and can be as effective as traditional region-of-interest (ROI) measurements of relative cerebral blood volume (rCBV), an operator-dependent method. We compare the routine ROI method with histogram analysis in the grading of glial neoplasms. MATERIALS AND METHODS: Ninety-two patients underwent conventional and DSC MR imaging. Routine rCBV (rCBVmax) measurements were obtained from ROIs of the maximal abnormality within the glioma. Histogram analysis rCBVT was performed with an ROI drawn around the maximal tumor diameter. Spearman rank correlations measured associations among glioma grade, rCBVmax, and histogram measures. Mann-Whitney tests compared grade with respect to rCBV and histogram measures. Logistic regression and McNemar test compared the utility of rCBVmax and histogram measures for detecting high grade gliomas. RESULTS: Routine rCBVmax analysis showed significant correlation with grade (r = 0.734, P < .001). Histogram rCBVT metrics showed significant correlation with grade (P < .008); the 3 highest were rCBVT SD, SD50, and mean25 (r = 0.718, 0.684, and 0.683, respectively). Grade could be predicted by rCBVmax (P < .001) as well as rCBV(T) (P < .008). Three rCBVT histogram measures (SD, SD25, and SD50) detected high-grade glioma with significantly higher specificity than rCBVmax when the diagnostic tests were constrained to have at least 95% sensitivity. CONCLUSION: rCBVT histogram analysis is as effective as rCBVmax analysis in the correlation with glioma grade. Inexperienced operators may obtain perfusion metrics using histogram analyses that are comparable with those obtained by experienced operators using ROI analysis.
PMID: 17416835
ISSN: 0195-6108
CID: 72815

Correlation of diffusion tensor and dynamic perfusion MR imaging metrics in normal-appearing corpus callosum: support for primary hypoperfusion in multiple sclerosis

Saindane, A M; Law, M; Ge, Y; Johnson, G; Babb, J S; Grossman, R I
BACKGROUND AND PURPOSE: Hypoperfusion of the normal-appearing white matter in multiple sclerosis (MS) may be related to ischemia or secondary to hypometabolism from wallerian degeneration (WD). This study evaluated whether correlating perfusion and diffusion tensor imaging (DTI) metrics in normal-appearing corpus callosum could provide support for an ischemic mechanism for hypoperfusion. MATERIALS AND METHODS: Fourteen patients with relapsing-remitting MS (RRMS) and 17 control subjects underwent perfusion MR imaging and DTI. Absolute measures of cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) were calculated. Mean diffusivity (MD) and fractional anisotropy (FA) maps were computed from DTI data. After visual coregistration of perfusion and DTI images, regions of interest were placed in the genu, central body, and splenium of normal-appearing corpus callosum. Pearson product-moment correlation coefficients were calculated using mean DTI and perfusion measures in each region. RESULTS: In the RRMS group, CBF and CBV were significantly correlated with MD in the splenium (r = 0.83 and r = 0.63, respectively; both P < .001) and in the central body (r = 0.86 and r = 0.65, respectively; both P < .001), but not in the genu (r = 0.23 and 0.25, respectively; both P is nonsignificant). No significant correlations were found between MTT and DTI measures or between FA and any perfusion measure in the RRMS group. No significant correlations between diffusion and perfusion metrics were found in control subjects. CONCLUSION: In the normal-appearing corpus callosum of patients with RRMS, decreasing perfusion is correlated with decreasing MD. These findings are more consistent with what would be expected in primary ischemia than in secondary hypoperfusion from WD.
PMID: 17416836
ISSN: 0195-6108
CID: 72816

Deep gray matter perfusion in multiple sclerosis: dynamic susceptibility contrast perfusion magnetic resonance imaging at 3 T

Inglese, Matilde; Park, Sun-Jung; Johnson, Glyn; Babb, James S; Miles, Laura; Jaggi, Hina; Herbert, Joseph; Grossman, Robert I
OBJECTIVES: To assess the presence of perfusion abnormalities in the deep gray matter of patients with relapsing-remitting and primary progressive multiple sclerosis (MS) in comparison with healthy controls and to investigate the impact of perfusion impairment on clinical disability and fatigue. DESIGN: Survey. SETTING: Research-oriented hospital. Patients Twenty-two patients with MS and 11 age- and sex-matched healthy volunteers. Intervention Absolute cerebral blood flow, cerebral blood volume, and mean transit time were measured in the thalamus, putamen, and caudate nuclei. MAIN OUTCOME MEASURES: Decrease of cerebral blood flow in the deep gray matter of patients with MS and correlation between perfusion impairment and the severity of fatigue. RESULTS: The cerebral blood flow value averaged over the thalamus, putamen, and caudate nuclei was significantly lower in patients with primary progressive MS (P<.001) and in patients with relapsing-remitting MS (P = .01) compared with controls, and there was a trend for patients with primary progressive MS to have lower average cerebral blood flow than patients with relapsing-remitting MS (P = .06). With respect to cerebral blood volume, there was a significant difference between patients with primary progressive MS and controls (P<.001) and between the 2 groups of patients (P = .03) but not between patients with relapsing-remitting MS and controls (P>.30). The fatigue score was significantly correlated with cerebral blood flow (r = 0.4; P<.001) and cerebral blood volume (r = 0.5; P = .004). CONCLUSION: The decrease of tissue perfusion in the deep gray matter of patients with MS is associated with the severity of fatigue
PMID: 17296835
ISSN: 0003-9942
CID: 70830

Reproducibility of three whole-brain N-acetylaspartate decline cohorts in relapsing-remitting multiple sclerosis

Gonen, O; Oberndorfer, T A; Inglese, M; Babb, J S; Herbert, J; Grossman, R I
BACKGROUND AND PURPOSE: The cross-sectional rate of whole-brain N-acetylaspartate (NAA, a neuronal cell marker) loss in clinically similar relapsing-remitting multiple sclerosis (RRMS) patients has recently been shown to fall into 3 distinct decline rate strata. Our goal was to test the reproducibility of this observation in a new cohort of RRMS patients. MATERIALS AND METHODS: Sixteen serial patients (12 women, 4 men, median age 38 [27-55] years) with clinically definite RRMS for an average of 5 (0.3-18) years' disease duration and a mean Expanded Disability Status Score of 2.0 (0-6) were studied, once each. Their whole-brain NAA (WBNAA) amounts, obtained with proton MR spectroscopy, were divided by brain volumes (segmented from MR imaging) to yield concentrations suitable for cross-sectional comparisons. RESULTS: Three distinct strata of cross-sectional NAA decline rates were found: -0.031, -0.32, and -1.71 mmol/L/y when disease duration was estimated from confirmed diagnosis, or -0.057, -0.20, and -1.38 mmol/L/y when measured from the first clinical symptom. These rates and their corresponding fractions of the study population were indistinguishable from those reported previously in a different group of 49 clinically similar (mean Expanded Disability Status Score also 2.0) RRMS patients. CONCLUSION: Reproducing the previous cohort's cross-sectional WBNAA decline characteristics in this new group of clinically similar RRMS patients indicates that 3 WBNAA loss strata may be a general attribute of MS. Consequently, WBNAA could serve as a surrogate marker for the global load of neuronal and axonal dysfunction and damage in this disease
PMID: 17296992
ISSN: 0195-6108
CID: 70829

Distal lower extremity imaging: prospective comparison of 2-dimensional time of flight, 3-dimensional time-resolved contrast-enhanced magnetic resonance angiography, and 3-dimensional bolus chase contrast-enhanced magnetic resonance angiography

Hahn, Winnie Y; Hecht, Elizabeth M; Friedman, Barak; Babb, James S; Jacobowitz, Glenn R; Lee, Vivian S
OBJECTIVE: To compare the 2-dimensional time of flight, the 3-dimensional time-resolved contrast-enhanced magnetic resonance (MR) angiography, and the 3-dimensional 3-station bolus chase contrast-enhanced MR angiography in assessing distal station atherosclerosis. METHODS: Two-dimensional time of flight, 3-dimensional time-resolved contrast-enhanced MR angiography, and 3-dimensional bolus chase contrast-enhanced MR angiography were performed from the knees to the metatarsal heads of 40 patients. Blinded to the patients' identity, 2 readers independently reviewed the 3 sequences in random order; differences were resolved by consensus. Anterior tibial, peroneal, and posterior tibial arterial lengths to the talar dome were scored as follows: 1, greater than 50% of the length of a normal artery; 2, less than 50%; and 3, total occlusion. Stenoses were scored as follows: 1, less than 50%; and 2, greater than 50%. The pedal vessels (dorsalis pedis, posterior tibial, and plantar pedal arch arteries) were scored as follows: 1, less than 50% stenosis; and 2, greater than 50% stenosis. The reference standard was a combined interpretation of all 3 sequences by both readers in consensus. RESULTS: For the 240 calf segments scored for length, concordance with reference assessment was poorer for the time of flight than for either the bolus chase or time-resolved angiography (P = 0.0021 and P = 0.0082, respectively), and the latter two were statistically indistinguishable. For stenosis grading of the 461 calf and pedal segments, the time-resolved and bolus chase methods were superior to the time of flight (P = <0.0001 and P = 0.0041, respectively), and the contrast-enhanced methods were statistically indistinguishable. CONCLUSIONS: Both contrast-enhanced time-resolved and bolus chase MR angiography are superior to the time of flight in diagnosing distal station peripheral vascular disease
PMID: 17259830
ISSN: 0363-8715
CID: 96614