Faculty Bibliography

This study aimed to determine regional pattern of tissue perfusion in the normal-appearing white matter (NAWM) of patients with primary-progressive (PP), relapsing-remitting (RR) multiple sclerosis (MS) and healthy controls, and to investigate the association between perfusion abnormalities and clinical disability. Using dynamic susceptibility contrast (DSC) perfusion MRI at 3 T, we studied 22 patients with clinically definite MS, 11 with PP-MS and 11 with RR-MS and 11 age- and gender-matched healthy volunteers. The MRI protocol included axial dual-echo, dynamic susceptibility contrast enhanced (DSC) T2*-weighted and post-contrast T1-weighted images. Absolute cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were measured in the periventricular, frontal, occipital NAWM and in the splenium of the corpus callosum. Compared to controls, CBF and CBV were significantly lower in all NAWM regions in both PP-MS patients (p values from <0.0001 to 0.001) and RR-MS (p values from <0.0001 to 0.020). Compared to RR-MS, PP-MS patients showed significantly lower CBF in the periventricular NAWM (p=0.002) and lower CBV in the periventricular and frontal NAWM (p values: 0.0029 and 0.022). EDSS was significantly correlated with the periventricular CBF (r=-0.48, p=0.0016) and with the periventricular and frontal CBV (r=-0.42, p=0.015; r=-0.35, p=0.038, respectively). This study suggests that the hemodynamic abnormalities of NAWM have clinical relevance in patients with MS. DSC perfusion MRI might provide a relevant objective measure of disease activity and treatment efficacy

OBJECTIVE: The aim of this study was to compare the quality of images obtained with fast 3D T2-weighted turbo spin-echo (TSE) MR cholangiopancreatography (MRCP) sequences and 1-mm isotropic voxels with the quality of conventional 2D MRCP images. SUBJECTS AND METHODS: Thirty consecutively registered patients (14 women, 16 men; average age, 60.2 years; age range, 32-87 years) underwent imaging at 1.5 T with a 6-element body array coil. All imaging was performed with three MRCP techniques: free-breathing 3D T2-weighted TSE (TR/TE, 1,300/680; flip angle, 180 degrees; field of view, 250-300 mm; matrix size, 256 x 256; slice thickness, 1 mm; parallel acquisition technique factor, 2); breath-hold 3D T2-weighted TSE (same parameters as the free-breathing 3D technique); breath-hold coronal and oblique coronal thick-slab 2D TSE without parallel acquisition technique (2,800/1,100; flip angle, 150-180 degrees). Quantitative measures of image signal and contrast were evaluated by analysis of variance and paired Student's t tests. A 5-point scale (1, nondiagnostic, to 5, high diagnostic confidence) was used to compare the 3D and 2D data sets for image quality and definition of biliary and pancreatic ductal anatomic features. Friedman's nonparametric and Wilcoxon's rank sum tests were performed for statistical analysis of the qualitative assessments. RESULTS: Quantitative results showed free-breathing and breath-hold 3D TSE images had significantly higher relative signal intensity and contrast than 2D TSE images (p < 0.0001). The qualitative findings showed that both free-breathing and breath-hold 3D TSE techniques gave better delineation of biliary anatomy (p < 0.0001) than the 2D technique. The overall quality of 3D images was better than that of 2D images, and 3D imaging was better at depicting pancreatic ducts, although the difference did not reach statistical significance. CONCLUSION: Three-dimensional volumetric MRCP images are of superior quality and give better delineation of pancreaticobiliary anatomy than conventional 2D images and have the added advantage of multiplanar and postprocessing capabilities

PURPOSE/OBJECTIVES: To identify potential factors that place patients with cancer at risk for unplanned readmissions after discharge from the hospital. DESIGN: Retrospective, descriptive, medical record review. SETTING: A National Cancer Institute-designated comprehensive cancer center in an urban area of the Northeastern United States. SAMPLE: 78 patients were selected from those readmitted within seven days of discharge. For each readmission case, a nonreadmitted patient was randomly selected and matched on discharge date and reason for prior admission. The age range was 22-87 years, men and women were equally represented, and 88% were Caucasian. METHODS: The Readmission Criteria Record was developed to collect data from medical records about factors associated with readmission, including demographics, severity of illness, support at home, symptoms, and comorbidities. MAIN RESEARCH VARIABLES: Criteria associated with readmission risk. FINDINGS: Patients who had gastrointestinal cancer, nausea within 24 hours of discharge, financial and insurance concerns, or caregiver difficulty or those who lived alone were more likely to be readmitted within seven days of discharge. Patients were more likely to be readmitted on Friday than any other day. Among readmitted patients, 48% were readmitted within one to two days postdischarge. CONCLUSIONS: Knowledge of factors that may place patients with cancer at an increased risk for readmission and subsequent implementation of appropriate interventions during hospitalization may help to decrease risk of readmission. IMPLICATIONS FOR NURSING: The factors identified provide a basis for assessment, planning, interventions, and follow-up of patients to help reduce the risk of readmission and, thus, poor outcomes

Transgenic mouse models have been essential for understanding the pathogenesis of Alzheimer's disease (AD) including those that model the deposition process of beta-amyloid (Abeta). Several laboratories have focused on research related to the non-invasive detection of early changes in brains of transgenic mouse models of Alzheimer's pathology. Most of this work has been performed using regional image analysis of individual mouse brains and pooling the results for statistical assessment. Here we report the implementation of a non-linear image registration algorithm to register anatomical and transverse relaxation time (T2) maps estimated from MR images of transgenic mice. The algorithm successfully registered mouse brain magnetic resonance imaging (MRI) volumes and T2 maps, allowing reliable estimates of T2 values for different regions of interest from the resultant combined images. This approach significantly reduced the data processing and analysis time, and improved the ability to statistically discriminate between groups. Additionally, 3D visualization of intra-regional distributions of T2 of the resultant registered images provided the ability to detect small changes between groups that otherwise would not be possible to detect

PURPOSE: To quantify, with three-dimensional proton magnetic resonance (MR) spectroscopy, metabolic characteristics of normal-appearing white matter and nonenhancing lesions in patients with relapsing-remitting multiple sclerosis (MS). MATERIALS AND METHODS: Institutional review board approval and informed patient consent were obtained. Nine patients with relapsing-remitting MS (six women, three men) and nine age-matched control subjects (seven women, two men) were studied with T1- and T2-weighted MR imaging and three-dimensional proton MR spectroscopy at spatial resolution less than a cubic centimeter. Absolute N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) levels were obtained from 171 voxels: 66 from lesions on T2-weighted MR images (43 hypointense and 23 isointense on T1-weighted MR images), 31 from normal-appearing white matter, and 74 from analogous normal white matter regions on images in control subjects. RESULTS: Mean NAA level in hypointense lesions (5.30 mmol/L +/- 2.27 [standard deviation]) was significantly lower (P < or = .05) than that in isointense lesions (7.82 mmol/L +/- 2.28), normal-appearing white matter (7.37 mmol/L +/- 1.71), and normal white matter in control subjects (8.89 mmol/L +/- 1.54). Cho (1.79 mmol/L +/- 0.65) and Cr (5.64 mmol/L +/- 1.50) levels in isointense lesions were indistinguishable from those in normal-appearing white matter (1.74 mmol/L +/- 0.46 and 4.99 mmol/L +/- 0.97, respectively) but were significantly higher (Cho, 20%; Cr, 24%) than those in normal white matter in control subjects (1.44 mmol/L +/- 0.40 and 4.30 mmol/L +/- 1.32, respectively). NAA, Cho, and Cr levels in normal-appearing white matter were significantly different than those in normal white matter in control subjects (NAA, 20% lower; Cho, 14% higher; and Cr, 17% higher). CONCLUSION: Abnormal metabolic activity persists in all MS tissue types. Increased Cr and Cho levels suggest (a) ongoing gliosis and attempted remyelination in isointense lesions on T1-weighted MR images and (b) membrane turnover (de- and remyelination), in addition to increased cellularity (gliosis, inflammation) in normal-appearing white matter

BACKGROUND: Anatomic and mucosal obstruction of the frontal sinus outflow tract (FSOT) can result in frontal sinusitis often associated with frontal headache. Thorough evaluation of symptomatic patients requires axial and coronal computerized tomographic (CT) scans of the paranasal sinuses (PNS). With the advent of multichannel multidetector CT scanning, the availability of high-quality sagittal images has become increasingly widespread. However, the utility of these images in the assessment of FSOT patency has not yet been established. METHODS: A retrospective review of coronal and sagittal images from 25 PNS CT scans (50 sides) were randomized, blinded, and independently evaluated by two neuroradiologists. FSOT obstruction by agger nasi cells, the ethmoid bulla, and mucosal disease was assessed. A degree of confidence was rendered for each of these findings. The results were then compared against a consensus diagnosis, which was rendered based upon simultaneous reading of the coronal and sagittal images. Generalized estimating equations were used to assess the difference between sagittal and coronal images in terms of reader confidence and diagnostic concordance with the consensus. RESULTS: Review of sagittal images had a higher degree of concordance with the consensus than did coronal images, and was highest for mucosal disease. Both readers were more confident in rendering a diagnosis based upon the sagittal images. CONCLUSION: Sagittal reformatted CT images of the PNS are helpful in the radiologic evaluation of the FSOT. Experienced neuroradiologists had a higher degree of confidence in the diagnosis of the obstruction of the FSOT using sagittal reformatted images

BACKGROUND AND PURPOSE: Perfusion measurement in multiple sclerosis (MS) may cast light on the disease pathogenesis and lesion development since vascular pathology is frequently demonstrated in the disease. This study was performed to investigate the perfusion characteristics in MS lesions using dynamic susceptibility contrast MR imaging (DSC-MRI) to better understand the hemodynamic changes in MS. METHODS: Seventeen patients with relapsing-remitting MS were studied with DSC-MRI. Perfusion measurements included cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT), were obtained in enhancing, non-enhancing lesions covered by DSC-MRI and contralateral normal appearing white matter (NAWM) in patients as well as normal white matter in seventeen control subjects. RESULTS: DSC-MRI data demonstrated reduced perfusion with significantly prolonged MTT (P < 0.001) in lesions and NAWM in patients compared with normal white matter in controls. Compared to contralateral NAWM, enhancing lesions demonstrate increased CBF (P = 0.007) and CBV (P < 0.0001), indicating inflammation-mediated vasodilatation. A K means cluster analysis was performed and identifies approximately 63.8% of non-enhancing lesions (Class 1) with significantly decreased perfusion (P < or = 0.0001) when compared with contralateral NAWM. In contrast, the remainder 36.2% non-enhancing lesions (Class 2) show increased CBV (P = 0.02) in a similar fashion to enhancing lesions and can be observed on quantitative color-coded maps even without blood-brain barrier breakdown. CONCLUSION: DSC-MRI measurements demonstrate potential for investigating hemodynamic abnormalities that are associated with inflammatory activity, lesion reactivity and vascular compromise in MS lesions. Non-enhancing lesions showed both low and high perfusion suggesting microvascular abnormalities with hemodynamic impairment and inflammatory reactivity that cannot be seen on conventional MRI

PURPOSE: To retrospectively determine whether differential temporal changes in signal intensity of the vertebral arteries, measured at a bolus-timing examination with a test dose of a gadolinium-based contrast agent, are present in patients with subclavian steal syndrome. MATERIALS AND METHODS: Institutional review board exemption was obtained, and informed consent was not required for this retrospective study. The study complied with the Health Insurance Portability and Accountability Act. Twenty-five patients with known or clinically suspected atherosclerotic disease of the aortic arch and branch vessels underwent breath-hold contrast material-enhanced magnetic resonance (MR) angiography with circulation time derived from a timing examination by using a test bolus of a gadolinium-based contrast agent. Eight patients (three men and five women aged 54-80 years; mean, 70 years) had subclavian stenosis or occlusion with retrograde vertebral artery flow confirmed with time-of-flight MR angiography, nine patients (eight men and one woman aged 31-91 years; mean, 70 years) had mild to severe ostial stenosis of a single vertebral artery, and eight patients (including four men and four women aged 53-86 years; mean, 73 years) had normal vertebral arteries. The difference in time to peak signal intensity between the right and left vertebral arteries was compared among the three groups by using Fisher exact and Cochran-Mantel-Haenszel tests. RESULTS: The delay in peak enhancement in the ipsilateral vertebral artery ranged from 2 to 4 seconds (mean, 2.5 seconds) in all eight patients with subclavian steal syndrome. In eight of nine patients with ostial vertebral artery stenosis and eight controls, both vertebral arteries filled simultaneously. The presence of unilateral delayed vertebral artery enhancement was significantly associated with retrograde flow in patients with subclavian steal syndrome, compared with patients with normal flow (P < .01) and those with ostial vertebral artery stenosis (P < .01). CONCLUSION: A bolus-timing examination performed with a test bolus of the gadolinium-based contrast agent via the neck vessels that demonstrates at least a 2-second delay in peak contrast enhancement in the right or left vertebral arteries may, in the appropriate clinical setting, indicate subclavian steal syndrome

PURPOSE: Ionizing radiation therapy (RT) is an important component in the management of breast cancer. Although the primary tumor can be successfully treated by surgery and RT, metastatic breast cancer remains a therapeutic challenge. Here we tested the hypothesis that the combination of RT to the primary tumor with CTLA-4 blockade can elicit antitumor immunity inhibiting the metastases.EXPERIMENTAL DESIGN: The poorly immunogenic metastatic mouse mammary carcinoma 4T1 was used as a model. Mice were injected s.c. with 4T1 cells, and treatment was started 13 days later when the primary tumors measured 5 mm in average diameter. Mice were randomly assigned to four treatment groups receiving: (1) control IgG (IgG), (2) RT + IgG, (3) 9H10 monoclonal antibody against CTLA-4, (4) RT + 9H10. RT was delivered to the primary tumor by one or two fractions of 12 Gy. 9H10 and IgG were given i.p. thrice after RT.RESULTS: Consistent with the fact that 4T1 is poorly immunogenic, 9H10 alone did not have any effect on primary tumor growth or survival. RT was able to delay the growth of the primary irradiated tumor, but in the absence of 9H10 survival was similar to that of control mice. In contrast, mice treated with RT + 9H10 had a statistically significant survival advantage. The increased survival correlated with inhibition of lung metastases formation and required CD8+ but not CD4+ T cells.CONCLUSIONS: The combination of local RT with CTLA-4 blockade is a promising new immunotherapeutic strategy against poorly immunogenic metastatic cancers

BACKGROUND AND PURPOSE: Patients with nonlesional temporal lobe epilepsy have long been known to have abnormalities of memory. Recently, these patients have been shown to have increased diffusivity in the hippocampus. We hypothesized that in these patients, a negative correlation would exist between diffusivity measures of the mesial temporal lobe and performance on neuropsychological tests. METHODS: Twenty presurgical patients with temporal lobe epilepsy and 20 age- and sex-matched healthy controls underwent MR imaging of the brain. Apparent diffusion coefficient region of interest measures were taken in both hippocampi and parahippocampal gyri by 2 independent observers. Mean whole brain diffusivity was calculated. All patients completed neuropsychological testing. Electroencephalogram and pathology results were collected. Patients and controls were compared with respect to each apparent diffusion coefficient measure. In patients, apparent diffusion coefficients ipsilateral and contralateral to the seizure focus were compared. Associations were assessed between diffusivity measures and neuropsychological scores. RESULTS: Eleven patients had right-sided seizure foci and 9 had left-sided seizure foci. Patients demonstrated higher apparent diffusion coefficient values than controls over the whole brain, in the hippocampi, and in the parahippocampal gyri (P < .05). Patients demonstrated higher apparent diffusion coefficient within the ipsilateral hippocampus (1.19 +/- 0.22 x 10(-3) s/mm2) and parahippocampal gyrus (1.02 +/- 0.12 x 10(-3) s/mm2) compared with the contralateral side (1.02 +/- 0.16 x 10(-3) s/mm2 and 0.96 +/- 0.09 x 10(-3) s/mm2, respectively) (P < .05). Negative correlations were seen between hippocampal apparent diffusion coefficients and multiple memory tests (P < .05). CONCLUSION: Quantitative diffusion measurements in the hippocampus correlate with memory dysfunction in patients with temporal lobe epilepsy