Faculty Bibliography

BACKGROUND AND PURPOSE: The Alberta Stroke Program Early CT Score (ASPECTS) is a reliable method of delineating the extent of middle cerebral artery (MCA) stroke. Our aim was to retrospectively compare the accuracy of ASPECTS on noncontrast CT, CT angiography (CTA) source images, and CT perfusion maps of cerebral blood volume (CBV) during the first 3 hours of middle cerebral artery (MCA) stroke. MATERIALS AND METHODS: First-time patients with MCA stroke who presented <3 hours from symptom onset and were evaluated by noncontrast CT/CTA/CT perfusion, had confirmed acute nonlacunar MCA infarct on diffusion-weighted MR imaging (DWI) within 7 days, and had follow-up angiography were included. Patients were excluded for persistent MCA occlusion or stenosis. Two raters through consensus assigned an ASPECTS on the noncontrast CT, CTA source images, and the section-selective (2 x 12 mm coverage) CT perfusion CBV maps. ASPECTS on follow-up DWI served as the reference standard. For each CT technique, the detection rates of regional infarction, the mean ASPECTS, and the linear correlation to final ASPECTS were determined and compared. P values <.05 were considered significant. RESULTS: Twenty-eight patients satisfied the criteria with DWI performed at a mean of 50.3 hours (range, 22-125 hours) post-CT imaging. Of 280 ASPECTS regions, 100 were infarcted on DWI. The accuracy of noncontrast CT, CTA source images, and CT perfusion CBV for detecting regional infarct was 80.0%, 84.3%, and 96.8%, respectively (P < .0001). The mean ASPECTSs of noncontrast CT, CTA source images, CT perfusion CBV, and DWI were 8.4 +/- 1.8, 8.0 +/- 1.8, 6.8 +/- 1.9, and 6.5 +/- 1.8, respectively. The mean noncontrast CT and CTA source image ASPECTS was different from that of DWI (P < .05). Correlation of noncontrast CT, CTA source images, and CT perfusion CBV ASPECTS with final ASPECTS was r(2) = 0.34, r(2) = 0.42, and r(2) = 0.91, respectively. CONCLUSION: In a retrospective cohort of MCA infarcts imaged <3 hours from stroke onset, ASPECTS was most accurately determined on CT perfusion CBV maps

Since the amino acid derivative N-acetylaspartate (NAA) is almost exclusive to neuronal cells in the adult mammalian brain and its concentration has shown local (or global) abnormalities in most focal (or diffuse) neurological diseases, it is considered a specific neuronal marker. Yet despite its biological and clinical prominence, the relative NAA concentration in the gray and white matter (GM, WM) remains controversial, with each reported to be higher than, equal to, or less than the other. To help resolve the controversy and importantly, access the NAA in both compartments in their entirety, we introduce a new approach to distinguish and quantify the whole-brain average GM and WM NAA concentration by integrating MR-image segmentation, localized and non-localized quantitative (1)H-MRS. We demonstrate and validate the method in ten healthy volunteers (5 women) 27+/-6 years old (mean+/-standard-deviation) at 1.5T. The results show that the healthy adult human brain comprises significantly less WM, 39+/-3%, than GM 60+/-4% by volume (p<0.01). Furthermore, the average NAA concentration in the WM, 9.5+/-1.0 mM, is significantly lower than in GM, 14.3+/-1.1 mM (p<0.01)

The purposes of this study were to develop a semiautomated cardiac contour segmentation method for use with cine displacement-encoded MRI and evaluate its accuracy against manual segmentation. This segmentation model was designed with two distinct phases: preparation and evolution. During the model preparation phase, after manual image cropping and then image intensity standardization, the myocardium is separated from the background based on the difference in their intensity distributions, and the endo- and epi-cardial contours are initialized automatically as zeros of an underlying level set function. During the model evolution phase, the model deformation is driven by the minimization of an energy function consisting of five terms: model intensity, edge attraction, shape prior, contours interaction, and contour smoothness. The energy function is minimized iteratively by adaptively weighting the five terms in the energy function using an annealing algorithm. The validation experiments were performed on a pool of cine data sets of five volunteers. The difference between the semiautomated segmentation and manual segmentation was sufficiently small as to be considered clinically irrelevant. This relatively accurate semiautomated segmentation method can be used to significantly increase the throughput of strain analysis of cine displacement-encoded MR images for clinical applications

Recruitment of effector T cells to inflamed peripheral tissues is regulated by chemokines and their receptors, but the factors regulating recruitment to tumors remain largely undefined. Ionizing radiation (IR) therapy is a common treatment modality for breast and other cancers. Used as a cytocidal agent for proliferating cancer cells, IR in combination with immunotherapy has been shown to promote immune-mediated tumor destruction in preclinical studies. In this study we demonstrate that IR markedly enhanced the secretion by mouse and human breast cancer cells of CXCL16, a chemokine that binds to CXCR6 on Th1 and activated CD8 effector T cells, and plays an important role in their recruitment to sites of inflammation. Using a poorly immunogenic mouse model of breast cancer, we found that irradiation increased the migration of CD8(+)CXCR6(+) activated T cells to tumors in vitro and in vivo. CXCR6-deficient mice showed reduced infiltration of tumors by activated CD8 T cells and impaired tumor regression following treatment with local IR to the tumor and Abs blocking the negative regulator of T cell activation, CTLA-4. These results provide the first evidence that IR can induce the secretion by cancer cells of proinflammatory chemotactic factors that recruit antitumor effector T cells. The ability of IR to convert tumors into 'inflamed' peripheral tissues could be exploited to overcome obstacles at the effector phase of the antitumor immune response and improve the therapeutic efficacy of immunotherapy

OBJECTIVE: The objective of our study was to retrospectively compare the degree of pelvic organ prolapse shown on dynamic true fast imaging with steady-state precession (FISP) versus HASTE sequences in symptomatic patients. MATERIALS AND METHODS: Fifty-nine women (mean age, 57 years) with suspected pelvic floor dysfunction underwent MRI using both a sagittal true FISP sequence, acquired continuously during rest alternating with the Valsalva maneuver, and a sagittal HASTE sequence, acquired sequentially at rest and at maximal strain. Data sets were evaluated in random order by two radiologists in consensus using the pubococcygeal line (PCL) as a reference. Measurement of prolapse was based on a numeric grading system indicating severity as follows: no prolapse, 0; mild, 1; moderate, 2; or severe, 3. A comparison between sequences on a per-patient basis was performed using a Wilcoxon's analysis with p < 0.05 considered significant. RESULTS: Overall, 66.1% (39/59) of patients had more severe prolapse (>or= 1 degrees ) based on dynamic true FISP images, with 28.8% (17/59) of the cases of prolapse seen exclusively on true FISP images. Only 20.3% (12/59) of patients had greater degrees of prolapse on HASTE images than on true FISP images, with 10.2% (6/59) of the cases seen exclusively on HASTE images. A statistically significant increase in the severity of cystoceles (p < 0.01) and urethral hypermobility (p < 0.01)-with a trend toward more severe urethroceles (p < 0.07), vaginal prolapse (p < 0.09), and rectal descent (p < 0.06)-was shown on true FISP images. CONCLUSION: Overall, greater degrees of organ prolapse in all three compartments were found with a dynamic true FISP sequence compared with a sequential HASTE sequence. Near real-time continuous imaging with a dynamic true FISP sequence should be included in MR protocols to evaluate pelvic floor dysfunction in addition to dynamic multiplanar HASTE sequences

OBJECTIVES: This study aimed to examine whether pediatric autoimmune neuropsychiatric disorders associated with streptococcus were appropriately diagnosed in the community and to determine subsequent rates of unwarranted use of antibiotic treatment for tics and obsessive-compulsive symptoms without the identification of an infection. METHODS: The design was a retrospective, cross-sectional, observational study of 176 children and adolescents who were evaluated in a specialty program for tics, Tourette's disorder, and related problems. Previously published diagnostic criteria were used to establish the diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcus in our clinic. RESULTS: Subjects were significantly less likely to receive a diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcus at the specialty clinic than in the community. In the community, subjects were significantly more likely to be treated with antibiotics or immunosuppressant medication if they received a diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcus. Of the 27 subjects with a community diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcus who were treated with antibiotics, 22 (82%) were treated without laboratory evidence of an infection; 2 were treated with immunomodulatory medications. CONCLUSIONS: Our results support our hypothesis that pediatric autoimmune neuropsychiatric disorders associated with streptococcus are frequently diagnosed in the community without the application of all working diagnostic criteria. This phenomenon has resulted in unwarranted use of antibiotic treatment for tics/obsessive-compulsive disorder without evidence of laboratory infection

PURPOSE: To quantify proton magnetic resonance (MR) spectroscopy-detectable metabolite concentrations along anteroposterior axis of hippocampus in healthy young and elderly subjects. MATERIALS AND METHODS: Young (three women, three men; age range, 25-35 years) and elderly (four women, two men; age range, 68-72 years) groups underwent MR imaging and proton MR spectroscopic imaging at 3 T in this HIPAA-compliant prospective study and gave institutional review board-approved written consent. Volume of interest was centered on and tilted parallel to hippocampal anteroposterior plane. Absolute N-acetylaspartate (NAA), choline, and creatine levels were obtained in each voxel, with phantom replacement. RESULTS: Mean NAA, creatine, and choline concentrations in the young group were higher in posterior hippocampus (12.9 mmol/L +/- 2.0 [standard deviation], 7.8 mmol/L +/- 1.2, 2.3 mmol/L +/- 0.4, respectively) than anterior hippocampus (8.0 mmol/L +/- 1.1, 6.0 mmol/L +/- 1.4, 1.5 mmol/L +/- 0.2; P = .005, .02, and .0002, respectively). In the elderly group, mean concentrations were higher in posterior hippocampus (8.6 mmol/L +/- 0.9, 5.6 mmol/L +/- 0.6, 1.5 mmol/L +/- 0.2, respectively) than anterior hippocampus (7.2 mmol/L +/- 1.0, 2.4 mmol/L +/- 0.3, 1.0 mmol/L +/- 0.2; P = .006, .0001, .04, respectively). Mean concentrations were significantly higher in the young group (13.2 mmol/L +/- 1.0, 7.4 mmol/L +/- 0.8, 2.1 mmol/L +/- 0.3, respectively) than in the elderly group (9.0 mmol/L +/- 1.0, 5.8 mmol/L +/- 0.8, 1.8 mmol/L +/- 0.3; P = .0001, .01, .05, respectively). Posteroanterior metabolic gradients differed: NAA decreased faster in the young group (-1.0 mmol/L x cm(-1)) than the elderly group (-0.7 mmol/L x cm(-1)); creatine and choline concentrations decreased faster in the elderly group (-0.8 and -0.058 mmol/L x cm(-1), respectively) than the young group (-0.16 and -0.008 mmol/L x cm(-1), respectively). No left-right metabolic differences were found. CONCLUSION: Significant metabolic heterogeneity was observed between groups and along anteroposterior axis of healthy hippocampus in both groups. Age matching and consistent voxel placement are important for correct comparisons of both absolute metabolic levels and metabolite ratios in longitudinal intra- and intersubject cross-sectional studies

PURPOSE: To characterize age-related MR diffusion patterns of the prefrontal brain cortex microstructure using a new method for investigating the non-Gaussian behavior of water diffusion called diffusional kurtosis imaging (DKI). MATERIALS AND METHODS: Measures of mean diffusivity (MD), fractional anisotropy (FA) and mean kurtosis (MK) were compared in the prefrontal brain cortex of 24 healthy volunteers (adolescents, young adults, and elderly) ranging from age 13 to 85 years. A Mann-Whitney test was used to compare subject groups with respect to the diffusion measures, and linear regression was used to characterize the change in each diffusion measure as a function of age. RESULTS: We found significant age-related changes in the elderly adult group, with increase of MD and decrease of FA. CONCLUSION: The current study demonstrates distinct mean kurtosis patterns for different age-ranges, with significant age-related correlation for mean kurtosis (MK) and MK peak position, showing that diffusional kurtosis is able to characterize and measure age-related diffusion changes for both grey and white matter, in the developing and aging brain

PURPOSE: To retrospectively determine whether relative cerebral blood volume (CBV) measurements can be used to predict clinical outcome in patients with high-grade gliomas (HGGs) and low-grade gliomas (LGGs) and specifically whether patients who have gliomas with a high initial relative CBV have more rapid progression than those who have gliomas with a low relative CBV. MATERIALS AND METHODS: Approval for this retrospective HIPAA-compliant study was obtained from the Institutional Board of Research Associates, with waiver of informed consent. One hundred eighty-nine patients (122 male and 67 female patients; median age, 43 years; range, 4-80 years) were examined with dynamic susceptibility-weighted contrast material-enhanced perfusion magnetic resonance (MR) imaging and were followed up clinically with MR imaging (median follow-up, 334 days). Log-rank tests were used to evaluate the association between relative CBV and time to progression by using Kaplan-Meier curves. Binary logistic regression was used to determine whether age, sex, and relative CBV were associated with an adverse event (progressive disease or death). RESULTS: Values for the mean relative CBV for patients according to each clinical response were as follows: 1.41 +/- 0.13 (standard deviation) for complete response (n = 4), 2.36 +/- 1.78 for stable disease (n = 41), 4.84 +/- 3.32 for progressive disease (n = 130), and 3.82 +/- 1.93 for death (n = 14). Kaplan-Meier estimates of median time to progression in days indicated that patients with a relative CBV of less than 1.75 had a median time to progression of 3585 days, whereas patients with a relative CBV of more than 1.75 had a time to progression of 265 days. Age and relative CBV were also independent predictors for clinical outcome. CONCLUSION: Dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging can be used to predict median time to progression in patients with gliomas, independent of pathologic findings. Patients who have HGGs and LGGs with a high relative CBV (>1.75) have a significantly more rapid time to progression than do patients who have gliomas with a low relative CBV